research on cancer treatment

Suggestions or feedback?

MIT News | Massachusetts Institute of Technology

• Machine learning
• Sustainability
• Black holes
• Classes and programs

Departments

• Aeronautics and Astronautics
• Brain and Cognitive Sciences
• Architecture
• Political Science
• Mechanical Engineering

Centers, Labs, & Programs

• Abdul Latif Jameel Poverty Action Lab (J-PAL)
• Picower Institute for Learning and Memory
• Lincoln Laboratory
• School of Architecture + Planning
• School of Engineering
• School of Humanities, Arts, and Social Sciences
• Sloan School of Management
• School of Science
• MIT Schwarzman College of Computing

New cancer treatment may reawaken the immune system

Press contact :, media download.

*Terms of Use:

Images for download on the MIT News office website are made available to non-commercial entities, press and the general public under a Creative Commons Attribution Non-Commercial No Derivatives license . You may not alter the images provided, other than to crop them to size. A credit line must be used when reproducing images; if one is not provided below, credit the images to "MIT."

Previous image Next image

Immunotherapy is a promising strategy to treat cancer by stimulating the body’s own immune system to destroy tumor cells, but it only works for a handful of cancers. MIT researchers have now discovered a new way to jump-start the immune system to attack tumors, which they hope could allow immunotherapy to be used against more types of cancer.

Their novel approach involves removing tumor cells from the body, treating them with chemotherapy drugs, and then placing them back in the tumor. When delivered along with drugs that activate T cells, these injured cancer cells appear to act as a distress signal that spurs the T cells into action.

“When you create cells that have DNA damage but are not killed, under certain conditions those live, injured cells can send a signal that awakens the immune system,” says Michael Yaffe, who is a David H. Koch Professor of Science, the director of the MIT Center for Precision Cancer Medicine, and a member of MIT’s Koch Institute for Integrative Cancer Research.

In mouse studies, the researchers found that this treatment could completely eliminate tumors in nearly half of the mice.

Yaffe and Darrell Irvine, who is the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and Materials Science and Engineering, and an associate director of the Koch Institute, are the senior authors of the study, which appears today in Science Signaling . MIT postdoc Ganapathy Sriram and Lauren Milling PhD ’21 are the lead authors of the paper.

T cell activation

One class of drugs currently used for cancer immunotherapy is checkpoint blockade inhibitors, which take the brakes off of T cells that have become “exhausted” and unable to attack tumors. These drugs have shown success in treating a few types of cancer but do not work against many others.

Yaffe and his colleagues set out to try to improve the performance of these drugs by combining them with cytotoxic chemotherapy drugs, in hopes that the chemotherapy could help stimulate the immune system to kill tumor cells. This approach is based on a phenomenon known as immunogenic cell death, in which dead or dying tumor cells send signals that attract the immune system’s attention.

Several clinical trials combining chemotherapy and immunotherapy drugs are underway, but little is known so far about the best way to combine these two types of treatment.

The MIT team began by treating cancer cells with several different chemotherapy drugs, at different doses. Twenty-four hours after the treatment, the researchers added dendritic cells to each dish, followed 24 hours later by T cells. Then, they measured how well the T cells were able to kill the cancer cells. To their surprise, they found that most of the chemotherapy drugs didn’t help very much. And those that did help appeared to work best at low doses that didn’t kill many cells.

The researchers later realized why this was so: It wasn’t dead tumor cells that were stimulating the immune system; instead, the critical factor was cells that were injured by chemotherapy but still alive.

“This describes a new concept of immunogenic cell injury rather than immunogenic cell death for cancer treatment,” Yaffe says. “We showed that if you treated tumor cells in a dish, when you injected them back directly into the tumor and gave checkpoint blockade inhibitors, the live, injured cells were the ones that reawaken the immune system.”

The drugs that appear to work best with this approach are drugs that cause DNA damage. The researchers found that when DNA damage occurs in tumor cells, it activates cellular pathways that respond to stress. These pathways send out distress signals that provoke T cells to leap into action and destroy not only those injured cells but any tumor cells nearby.

“Our findings fit perfectly with the concept that ‘danger signals’ within cells can talk to the immune system, a theory pioneered by Polly Matzinger at NIH in the 1990s, though still not universally accepted,” Yaffe says.  

Tumor elimination

In studies of mice with melanoma and breast tumors, the researchers showed that this treatment eliminated tumors completely in 40 percent of the mice. Furthermore, when the researchers injected cancer cells into these same mice several months later, their T cells recognized them and destroyed them before they could form new tumors.

The researchers also tried injecting DNA-damaging drugs directly into the tumors, instead of treating cells outside the body, but they found this was not effective because the chemotherapy drugs also harmed T cells and other immune cells near the tumor. Also, injecting the injured cells without checkpoint blockade inhibitors had little effect.

“You have to present something that can act as an immunostimulant, but then you also have to release the preexisting block on the immune cells,” Yaffe says.

Yaffe hopes to test this approach in patients whose tumors have not responded to immunotherapy, but more study is needed first to determine which drugs, and at which doses, would be most beneficial for different types of tumors. The researchers are also further investigating the details of exactly how the injured tumor cells stimulate such a strong T cell response.

The research was funded, in part, by the National Institutes of Health, the Mazumdar-Shaw International Oncology Fellowship, the MIT Center for Precision Cancer Medicine, and the Charles and Marjorie Holloway Foundation.

Share this news article on:

Related links.

• Department of Biology
• Department of Biological Engineering
• Department of Materials Science and Engineering
• Koch Institute
• Ragon Institute

Related Topics

• Biological engineering

Related Articles

Cancer biologists identify new drug combo

A boost for cancer immunotherapy

Fighting cancer with the power of immunity

Previous item Next item

More MIT News

Alex Shalek named director of the Institute for Medical Engineering and Science

Read full story →

New tool empowers pavement life-cycle decision-making while reducing data collection burden

A new model offers robots precise pick-and-place solutions

With sustainable cement, startup aims to eliminate gigatons of CO₂

3 Questions: Preparing students in MIT’s naval ROTC program

Going Dutch on climate

• More news on MIT News homepage →

Massachusetts Institute of Technology 77 Massachusetts Avenue, Cambridge, MA, USA

• Map (opens in new window)
• Events (opens in new window)
• People (opens in new window)
• Careers (opens in new window)
• Accessibility
• Social Media Hub
• MIT on Facebook
• MIT on YouTube
• MIT on Instagram

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Ecancermedicalscience

Innovative approaches for cancer treatment: current perspectives and new challenges

Carlotta pucci.

1 Smart Bio-Interfaces, Istituto Italiano di Tecnologia, 56025 Pisa, Italy

a https://orcid.org/0000-0002-8976-3711

Chiara Martinelli

b https://orcid.org/0000-0001-9360-1689

Gianni Ciofani

2 Department of Mechanical and Aerospace Engineering, Politecnico di Torino, 10129 Torino, Italy

c https://orcid.org/0000-0003-1192-3647

Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing ad hoc systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research.

Introduction

Cancer is one of the main causes of death worldwide, and in the past decade, many research studies have focused on finding new therapies to reduce the side effects caused by conventional therapies.

During cancer progression, tumours become highly heterogeneous, creating a mixed population of cells characterised by different molecular features and diverse responsivity to therapies. This heterogeneity can be appreciated both at spatial and temporal levels and is the key factor responsible for the development of resistant phenotypes promoted by a selective pressure upon treatment administration [ 1 ]. Usually, cancer is treated as a global and homogeneous disease and tumours are considered as a whole population of cells. Thus, a deep understanding of these complex phenomena is of fundamental importance in order to design precise and efficient therapies.

Nanomedicine offers a versatile platform of biocompatible and biodegradable systems that are able to deliver conventional chemotherapeutic drugs in vivo , increasing their bioavailability and concentration around tumour tissues, and improving their release profile [ 2 ]. Nanoparticles can be exploited for different applications, ranging from diagnosis to therapy [ 2 ].

Recently, extracellular vesicles (EVs), responsible for cancer development, microenvironment modification and required for metastatic progression, have been widely investigated as efficient drug delivery vehicles [ 3 ].

Natural antioxidants and many phytochemicals have been recently introduced as anti-cancer adjuvant therapies due to their anti-proliferative and pro-apoptotic properties [ 4 , 5 ].

Targeted therapy is another branch of cancer therapy aiming at targeting a specific site, such as tumour vasculature or intracellular organelles, leaving the surroundings unaffected. This enormously increases the specificity of the treatment, reducing its drawbacks [ 6 ].

Another promising opportunity relies on gene therapy and expression of genes triggering apoptosis [ 7 ] and wild type tumour suppressors [ 8 ], or the targeted silencing mediated by siRNAs, currently under evaluation in many clinical trials worldwide [ 9 ].

Thermal ablation of tumours and magnetic hyperthermia are opening new opportunities for precision medicine, making the treatment localised in very narrow and precise areas. These methods could be a potential substitute for more invasive practices, such as surgery [ 10 , 11 ].

Furthermore, new fields such as radiomics and pathomics are contributing to the development of innovative approaches for collecting big amounts of data and elaborate new therapeutic strategies [ 12 , 13 ] and predict accurate responses, clinical outcome and cancer recurrence [ 14 – 16 ].

Taken all together, these strategies will be able to provide the best personalised therapies for cancer patients, highlighting the importance of combining multiple disciplines to get the best outcome.

In this review, we will provide a general overview of the most advanced basic and applied cancer therapies, as well as newly proposed methods that are currently under investigation at the research stage that should overcome the limitation of conventional therapies; different approaches to cancer diagnosis and therapy and their current status in the clinical context will be discussed, underlining their impact as innovative anti-cancer strategies.

Nanomedicine

Nanoparticles are small systems (1–1,000 nm in size) with peculiar physicochemical properties due to their size and high surface-to-volume ratio [ 17 ]. Biocompatible nanoparticles are used in cancer medicine to overcome some of the issues related to conventional therapies, such as the low specificity and bioavailability of drugs or contrast agents [ 2 ]. Therefore, encapsulation of the active agents in nanoparticles will increase their solubility/biocompatibility, their stability in bodily fluids and retention time in the tumour vasculature [ 18 – 20 ]. Furthermore, nanoparticles can be engineered to be extremely selective for a precise target [ 21 , 22 ] (see the “Targeted therapy and immunotherapy” section) and to release the drug in a controlled way by responding to a specific stimulus [ 18 , 23 – 25 ]. This is the case of ThermoDox, a liposomal formulation that can release doxorubicin as a response to an increment of temperature [ 26 ].

Inorganic nanoparticles are generally used as contrast agents for diagnosis purposes. Among them, quantum dots are small light-emitting semiconductor nanocrystals with peculiar electronic and optical properties, which make them highly fluorescent, resistant to photobleaching and sensitive for detection and imaging purposes [ 27 ]. Combined with active ingredients, they can be promising tools for theranostic applications [ 27 ]. In a recent study, quantum dots coated with poly(ethylene glycol) (PEG) were conjugated to anti-HER2 antibody and localised in specific tumour cells [ 28 ].

Superparamagnetic iron oxide nanoparticles (SPIONs) are usually exploited as contrast agents in magnetic resonance imaging (MRI) because they interact with magnetic fields [ 29 , 30 ]. Five types of SPIONs have been tested for MRI: ferumoxides (Feridex in the US, Endorem in Europe), ferucarbotran (Resovist), ferucarbotran C (Supravist, SHU 555 C), ferumoxtran-10 (Combidex) and NC100150 (Clariscan). Ferucarbotran is currently available in few countries, while the others have been removed from the market [ 25 ]. SPIONs have also been studied for cancer treatment by magnetic hyperthermia (see the “Thermal ablation and magnetic hyperthermia” section), and a formulation of iron oxide coated with aminosilane called Nanotherm has been already approved for the treatment of glioblastoma [ 31 ].

Gold nanoparticles have raised interest because of their optical and electrical properties and low toxicity [ 32 – 34 ]. They are mainly used as contrast agents for X-ray imaging, computed tomography [ 25 ], photoacoustic imaging [ 35 ] and photodynamic therapy [ 36 ]. A nanoshell made of a silica core and a gold shell coated with PEG was approved by the Food and Drug Administration (FDA) in 2012 and commercialised as AuroShell (Nanospectra) for the treatment of breast cancer by photodynamic therapy [ 25 ].

Organic nanoparticles are mainly used as delivery systems for drugs. Liposomes and micelles are both made of phospholipids, but they differ in their morphology. Liposomes are spherical particles having at least one lipid bilayer, resembling the structure of cell membranes. They are mainly used to encapsulate hydrophilic drugs in their aqueous core, but hydrophobic drugs can also be accommodated in the bilayer or chemically attached to the particles [ 37 ]. Micelles, instead, own a hydrophobic core that can encapsulate hydrophobic drugs [ 38 ]. Doxil, doxorubicin-loaded PEGylated liposomes, were the first nanoparticles approved by the FDA in 1995 to treat AIDS-associated Kaposi’s sarcoma [ 39 ]. This formulation drastically reduces doxorubicin side effects. Since then, other liposomal formulations have been approved by the FDA for cancer therapy, such as Myocet and DaunoXome [ 40 – 42 ]. Polymeric nanoparticles are made of biocompatible or natural polymers, such as poly(lactide-co-glycolide), poly(ε-caprolactone), chitosan, alginate and albumin [ 43 ]. Some formulations have already been accepted by the FDA, such as Abraxane (albumin-paclitaxel particles for the treatment of metastatic breast cancer and pancreatic ductal adenocarcinoma) and Ontak (an engineered protein combining interleukin-2 and diphtheria toxins for the treatment of non-Hodgkin’s peripheral T-cell lymphomas).

As well as these systems, which have been either accepted or are under clinical investigation, it is worth mentioning some new nanoparticles currently undergoing testing at the research level, which should improve treatment performance. For example, solid lipid nanoparticles, made of lipids that are solid at body temperature [ 44 ], and fabricated to load hydrophobic drugs [ 45 ] have been demonstrated to give a higher drug stability and prolonged release compared to other systems; however, the encapsulation efficiency is often low because of their high crystallinity [ 46 ]. To overcome this issue, one or more lipids, liquid at room temperature (like oleic acid, for example), are included in the formulation [ 47 ]. Lipid nanoparticles are good candidates for brain tumour therapy as they are able to cross the blood–brain barrier (BBB) [ 48 ]. A recent work showed that lipid nanoparticles loaded with SPIONs and temozolomide are efficient to treat glioblastoma since they combine the effect of the conventional chemotherapy and hyperthermia [ 49 , 50 ]. Dendrimers are another family of nanoparticles composed of polymers with a repetitive branched structure and characterised by a globular morphology [ 51 , 52 ]. Their architecture can be easily controlled, making their structure extremely versatile for many applications. For example, some recent studies show that poly-L-lysine (PLL) dendrimers loaded with doxorubicin induce anti-angiogenic responses in in vivo tumour models [ 53 ]. Currently, there is only one clinical trial for a formulation named ImDendrim based on a dendrimer and on a rhenium complex coupled to an imidazolium ligand, for the treatment of inoperable liver cancers that do not respond to conventional therapies [ 54 ].

Extracellular vesicles for cancer diagnosis and therapy

EVs are classified in two categories based on their biogenesis. Specifically, exosomes are small vesicles of around 30–150 nm originated from endosomes in physiological and pathological conditions and released by a fusion of multivesicular bodies (MVBs) to the cell membrane [ 55 , 56 ], while shed microvesicles (sMVs), with a typical size of 50–1,300 nm, are present in almost any extracellular bodily fluid and are responsible for the exchange of molecular materials between cells [ 57 , 58 ]. Exosomes are involved in cancer development and spreading [ 3 , 59 , 60 ], in the bidirectional communication between tumour cells and surrounding tissues, and in the construction of the microenvironment needed for pre-metastatic niche establishment and metastatic progression [ 61 ]. Hence, circulating vesicles are clinically relevant in cancer diagnosis, prognosis and follow up. Exosomes are actually recognised as valid diagnostic tools, but they can also be isolated and exploited as anti-cancer vaccines or nanosized drug carriers in cancer therapy [ 62 ].

Nowadays, one of the main issues in cancer diagnosis is the early identification of biomarkers by non-invasive techniques. Obtaining a significant amount of information, before and during tumour treatment, should allow the monitoring of cancer progression and the efficacy of therapeutic regimens. Liquid biopsies to detect circulating tumour cells, RNAs, DNAs and exosomes have been used as indicators for personalised medicine [ 63 ]. In recent years, exosomes detection has been validated as a reliable tool for preclinical practice in different cancer types [ 64 ], thanks to the identification of their content: double-stranded DNA (dsDNA) [ 65 , 66 ], messenger RNA (mRNA), micro RNA (miRNA), long non-coding RNA (lncRNA) [ 67 ], proteins and lipids [ 68 ]. DsDNA has been detected in exosomes isolated from plasma and serum of different cancer cell types, and mutated genes involved in tumorigenesis, such as mutated KRAS and TP53 [ 69 , 70 ], have been identified as disease predictors. Similarly, exosomal AR-V7 mRNA has been used as a prognostic marker of resistance to hormonal therapy in metastatic prostate cancer patients [ 71 ]. Gene expression profiling of multiple RNAs from urinary exosomes has been adopted as an efficient diagnostic tool [ 72 ]. LncRNAs isolated from serum exosomes have been exploited for disease prognosis in colorectal cancer patients [ 73 ], and multiple miRNAs allow one to distinguish between different lung cancer subtypes [ 74 ]. GPC1-positive exosomes have been employed to detect pancreatic cancer [ 75 ], while circulating exosomal macrophage migration inhibitory factor (MIF) was able to predict liver metastasis onset [ 76 ]. Finally, multiple lipids present in urinary exosomes have been approved as prostate cancer indicators [ 77 ]. Due to the high variability of patient classes and sample size, and in order to obtain clinically significant results for a fast and effective diagnosis, huge investments in exosome research will be required in the near future.

Exosomes could also be exploited as natural, biocompatible and low immunogenic nanocarriers for drug delivery in cancer therapy. They can be passively loaded by mixing purified vesicles with small drugs [ 78 – 82 ], or actively loaded by means of laboratory techniques, such as electroporation and sonication [ 83 , 84 ]. Superparamagnetic nanoparticles conjugated to transferrin have been tested for the isolation of exosomes expressing transferrin receptor from mice blood. After incubation with doxorubicin, they have been used to target liver cancer cells in response to external magnetic fields, inhibiting cell growth both in vitro and in vivo [ 80 ]. Kim et al. [ 83 ] engineered mouse macrophage-derived exosomes with aminoethyl anisamide-PEG to target sigma receptor, overexpressed in lung cancer cells and passively loaded them with paclitaxel. These systems acted as targeting agents able to suppress metastatic growth in vivo .

Three clinical trials with loaded exosomes are currently ongoing for the treatment of different tumours [ 85 – 87 ]: a phase I trial is evaluating the ability of exosomes to deliver curcumin to normal and colon cancer tissues [ 85 ]; a phase II trial is investigating the in vivo performance of autologous tumour cell-derived microparticles carrying methotrexate in lung cancer patients [ 86 ] and a clinical inquiry is focusing on autologous erythrocyte-derived microparticles loaded with methotrexate for gastric, colorectal and ovarian cancer treatment [ 87 ].

Recently, new strategies to produce ad hoc exosomes have been developed. Cells releasing exosomes have been genetically engineered to overexpress specific macromolecules, or modified to release exosomes with particular targeting molecules [ 88 – 90 ].

Exosomes derived from different cancer cells have already been exploited as cancer vaccines. Autologous dendritic cell-derived exosomes with improved immunostimulatory function have been tested in a phase II clinical trial for the activation of CD8 + T cells [ 91 ] in non-small cell lung cancer (NSCLC) patients, observing disease stabilisation and a better overall survival [ 92 ]. In a phase I trial, ascites-derived exosomes supplemented with granulocyte-macrophage colony stimulating factor (GM-CSF) have been administered to colorectal cancer patients, soliciting a tumour-specific immune response [ 93 ].

Many issues related to exosomes clinical translation remain open and are mostly connected to the definition of preclinical procedures for isolation, quantification, storage and standard protocols for drug loading. It is becoming even more necessary to distinguish between tumour and healthy blood cell-derived vesicles to characterise their post-isolation half-life and to perform standard content analyses. For these purposes, innovative approaches and technologies have been set up, such as microarrays and specific monoclonal antibodies and RNA markers amplification strategies [ 94 ].

Natural antioxidants in cancer therapy

Every day, the human body undergoes several exogenous insults, such as ultraviolet (UV) rays, air pollution and tobacco smoke, which result in the production of reactive species, especially oxidants and free radicals, responsible for the onset of many diseases, including cancer. These molecules can also be produced as a consequence of clinical administration of drugs, but they are also naturally created inside our cells and tissues by mitochondria and peroxisomes, and from macrophages metabolism, during normal physiological aerobic processes.

Oxidative stress and radical oxygen species are able to damage DNA (genetic alterations, DNA double strand breaks and chromosomal aberrations [ 95 , 96 ]) and other bio-macromolecules [ 97 ], such as lipids (membrane peroxidation and necrosis [ 98 ]) and proteins (significantly changing the regulation of transcription factors and, as a consequence, of essential metabolic pathways [ 99 ]).

The protective mechanisms our body has developed against these molecules are sometimes insufficient to counteract the huge damages produced. Recently, in addition to research into the roles of the physiological enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GP), natural antioxidants such as vitamins, polyphenols and plant-derived bioactive compounds are being studied in order to introduce them as preventive agents and potential therapeutic drugs [ 100 , 101 ]. These molecules have anti-inflammatory and anti-oxidant properties and are found in many vegetables and spices [ 102 ]. Vitamins, alkaloids, flavonoids, carotenoids, curcumin, berberine, quercetin and many other compounds have been screened in vitro and tested in vivo , displaying appreciable anti-proliferative and pro-apoptotic properties, and have been introduced as complementary therapies for cancer [ 4 , 5 , 103 ].

Despite the advantages of using natural drugs, their translation into clinical practice remains difficult due to their limited bioavailability and/or toxicity. Curcumin, a polyphenolic compound extracted from turmeric ( Curcuma longa ), is a traditional Southeast Asian remedy with anti-inflammatory, anti-oxidant and chemopreventive and therapeutic activities [ 104 ]. It has been shown to have cytotoxic effects in different kinds of tumours, such as brain, lung, leukaemia, pancreatic and hepatocellular carcinoma [ 105 , 106 ], with no adverse effects in normal cells at the effective therapeutic doses [ 107 ]. Curcumin can modulate a plethora of cellular mechanisms [ 108 , 109 ]; however, its biological properties, and as a consequence, the treatment duration and the efficient therapeutic doses, have not been completely elucidated yet. This molecule is highly lipophilic, poorly soluble in water and not very stable [ 110 ]. Different strategies and specific carriers, such as liposomes and micelles [ 111 , 112 ], have been developed to improve its bioavailability. Currently, 24 clinical trials involving curcumin are ongoing and 23 have been already completed [ 113 ].

Berberine is an alkaloid compound extracted from different plants, such as Berberis . Recently, it has been demonstrated to be effective against different tumours and to act as a chemopreventive agent, modulating many signalling pathways [ 114 , 115 ]. Like curcumin, it is poorly soluble in water; therefore, different nanotechnological strategies have been developed to facilitate its delivery across cell membranes [ 116 – 119 ]; six clinical trials are open and one has been completed [ 120 ].

Quercetin, a polyphenolic flavonoid found in fruits and vegetable, has been proven to be effective to treat several tumours, such as lung, prostate, liver, colon and breast cancers [ 121 – 123 ], by binding cellular receptors and interfering with many signalling pathways [ 124 ]. Interestingly, it has been shown to be effective also in combination with chemotherapeutic agents [ 125 ]. Presently, seven clinical trials are open and four have been completed [ 126 ].

Targeted therapy and immunotherapy

One of the main problems of conventional cancer therapy is the low specificity of chemotherapeutic drugs for cancer cells. In fact, most drugs act both on healthy and diseased tissues, generating severe side effects. Researchers are putting a lot of effort into finding a way to target only the desired site. Nanoparticles have raised great interest for their tendency to accumulate more in tumour tissues due to the enhanced permeability and retention effect (EPR) [ 127 ]. This process, called passive targeting, relies on the small size of nanoparticles and the leaky vasculature and impaired lymphatic drainage of neoplastic tissues [ 6 ]. Passive targeting, however, is difficult to control and can induce multidrug resistance (MDR) [ 128 ]. Active targeting, on the other hand, enhances the uptake by tumour cells by targeting specific receptors that are overexpressed on them [ 129 , 130 ]. Nanoparticles, for example, can be functionalized with ligands that univocally bind particular cells or subcellular sites [ 6 ]. Several kinds of ligands can be used, such as small molecules, peptides, proteins, aptamers and antibodies.

Folic acid and biotin are small molecules, whose receptors are overexpressed in tumour tissues. Several nanocarriers have been functionalized with folic acid to target ovarian and endometrial cancers [ 131 ]: folic acid-conjugated polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles delivering docetaxel increased drug cellular uptake by human cervical carcinoma cells [ 132 ]. Small ligands are cheap and can be linked to nanoparticles by simple conjugation chemistry [ 133 , 134 ].

Different kinds of small peptides and proteins are also effective in active targeting. Angiopep-2 is a peptide that has raised great interest in the treatment of brain cancer [ 135 ], because it binds to low-density lipoprotein receptor-related protein-1 (LRP1) of endothelial cells in the BBB, and it is also overexpressed in glioblastoma cancer cells [ 136 ]. Bombesin peptide conjugated to poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with docetaxel was used to target the gastrin-releasing peptide receptor, overexpressed on cell surface of prostate, breast, ovarian, pancreatic and colorectal cancer cells [ 137 , 138 ]. Transferrin is a serum glycoprotein overexpressed on many solid tumours, especially on glioblastoma multiforme cells [ 139 ], and on epithelial cells of the BBB [ 6 , 140 ]. Transferrin-conjugated chitosan-PEG nanoparticles delivering paclitaxel exhibited a higher cytotoxicity towards transferrin-overexpressing human non-small cell lung cancer cells (NSCLCs) (HOP-62) [ 141 ].

Aptamers are small synthetic single-stranded RNA or DNA oligonucleotides folded into specific shapes that make them capable of binding specific targets [ 142 ]. Farokhzad et al. [ 143 ] reported that the use of A10 RNA aptamer conjugated to docetaxel-loaded nanoparticles significantly enhances in vitro cytotoxicity. The same aptamer has been also used to prepare quantum dot-doxorubicin conjugates [ 144 ].

Antibodies are currently the most exploited ligands for active targeting. These proteins have a typical ‘Y’ shape, where the two arms are responsible for the selective interaction with the antigen [ 145 ]. Antibodies can be used as immunoconjugates, when conjugated to a drug or nanoparticle, or naked. In the first case, their function is mainly to target a specific antigen overexpressed on cancer cells. Antibodies used for this purpose include those ones that bind to the human epidermal growth factor receptor 2 (HER2), the epidermal growth factor receptor (EGFR), the transferrin receptor (TfR) and the prostate-specific membrane antigen (PSMA) [ 6 ]. Rapamycin-PLGA nanoparticle conjugated to EGFR antibody exhibited higher cellular uptake by human breast adenocarcinoma cells (MCF-7), with enhanced apoptotic activity [ 146 ]. Loperamide-loaded human serum albumin nanoparticles conjugated to antibodies that specifically bind transferrin receptor successfully crossed the BBB and delivered the drug to the desired site [ 147 ].

Naked antibodies or immunoconjugates can also be used in immunotherapy, which is a cancer treatment that aims at stimulating or restoring the immune system of the patient against cancer cells [ 148 ]. Antibodies can act as markers for cancer cells to make them more vulnerable to the immune system response (non-specific immune stimulation), or as inhibitors for immune checkpoint proteins on cancer cell surface, that can modulate the action of T-cells [ 148 ]. Several antibodies have been already tested and accepted by FDA for immunotherapy, such as rituximab (1997, [ 149 ]), ibritumomab tiuxetan (2002, [ 150 ]), trastuzumab emtansine (2013, [ 151 ]), nivolumab (2014, [ 152 ]) and pembrolizumab (2014, [ 153 ]).

Immunotherapy can be achieved by another strategy called adoptive cell transfer (ACT) and it consists of isolating T-lymphocytes (T-cells) with the highest activity against cancer directly from the patient’s blood, expanding them ex vivo , and reinfusing them again into the patient [ 154 ]. Autologous T-cells can be genetically engineered in vitro to express a chimaeric antigen receptor (CAR), which makes them more specific against cancer cell antigens [ 148 ]. Different CARs can be designed to be directed against a certain cancer antigen. The genetic modification of T-cells can be achieved by different methods such as viral transduction, non-viral methods like DNA-based transposons, CRISPR/Cas9 or other plasmid DNA and mRNA transfer techniques (i.e., electroporation, encapsulation in nanoparticles) [ 155 ]. ACT protocols have been already adopted in clinical practice for advanced or recurrent acute lymphoblastic leukaemia and for some aggressive forms of non-Hodgkin’s lymphoma [ 148 ]. For example, it has been shown that the treatment of end-stage patients affected by acute lymphocytic leukaemia with CAR T-cells led to a full recovery in up to 92% of patients [ 155 ]. Despite these very promising results, much research is currently devoted to understanding the long-term side effects of CAR T-cell therapies and their fate within tumours, and to improving CAR T-cell expansion technologies.

Gene therapy for cancer treatment

Gene therapy is intended as the introduction of a normal copy of a defective gene in the genome in order to cure specific diseases [ 156 ]. The first application dates back to 1990 when a retroviral vector was exploited to deliver the adenosine deaminase (ADA) gene to T-cells in patients with severe combined immunodeficiency (SCID) [ 157 ]. Further research demonstrated that gene therapy could be applied in many human rare and chronic disorders and, most importantly, in cancer treatment. Approximately 2,900 gene therapy clinical trials are currently ongoing, 66.6% of which are related to cancer [ 158 ]. Different strategies are under evaluation for cancer gene therapy: 1) expression of pro-apoptotic [ 159 , 160 ] and chemo-sensitising genes [ 4 ]; 2) expression of wild type tumour suppressor genes [ 5 ]; 3) expression of genes able to solicit specific antitumour immune responses and 4) targeted silencing of oncogenes.

One approach relied on thymidine kinase (TK) gene delivery, followed by administration of prodrug ganciclovir to activate its expression and induce specific cytotoxicity [ 161 ]. This has been clinically translated for the treatment of prostate cancer and glioma [ 162 – 164 ]. In recent decades, different vectors carrying the p53 tumour suppressor gene have been evaluated for clinical applications. ONYX-015 has been tested in NSCLC patients and gave a high response rate when administered alone or together with chemotherapy [ 165 ]. Gendicine, a recombinant adenovirus carrying wild-type p53 in head and neck squamous cell cancer had a similar success, inducing complete disease regression when combined with radiotherapy [ 166 ].

Despite many achievements, there are still some challenges to face when dealing with gene therapy, such as the selection of the right conditions for optimal expression levels and the choice of the best delivery system to univocally target cancer cells. Gene therapy also presents some drawbacks linked to genome integration, limited efficacy in specific subsets of patients and high chances of being neutralised by the immune system. Therefore, particular interest has been elicited by targeted gene silencing approaches.

RNA interference (RNAi) has been recently established as an efficient technology both for basic research and medical translation. Small interfering RNAs (siRNAs) consist of double-stranded RNAs [ 167 ] able to produce targeted gene silencing. This process is intracellularly mediated by the RNA-induced silencing complex (RISC), responsible for cleaving the messenger RNA (mRNA), thus leading to interference with protein synthesis [ 168 ]. This physiological mechanism has been demonstrated in many eukaryotes, including animals. A few years after RNAi discovery, the first clinical application for wet-age related macular degeneration treatment entered phase I clinical trial [ 169 ]. Since cancer is triggered by precise molecular mechanisms, siRNAs can be rationally designed to block desired targets responsible for cell proliferation and metastatic invasion. This strategy relies on siRNA-mediated gene silencing of anti-apoptotic proteins [ 170 ], transcription factors (i.e., c-myc gene) [ 171 , 172 ] or cancer mutated genes (i.e., K-RAS ) [ 173 ]. Most of the clinical trials currently ongoing are based on local administration of siRNA oligonucleotides in a specific tissue/organ or on systemic delivery throughout the entire body [ 9 , 174 ]. Using siRNA-based drugs has several advantages: 1) safety, since they do not interact with the genome; 2) high efficacy, because only small amounts can produce a dramatic gene downregulation; 3) possibility of being designed for any specific target; 4) fewer side effects when compared to conventional therapies and 5) low costs of production [ 175 , 176 ]. However, siRNAs are relatively unstable in vivo and can be phagocytosed during blood circulation, excreted by renal filtration, or undergo enzymatic degradation [ 177 ]. Occasionally, they can induce off-target effects [ 178 ] or elicit innate immune responses, followed by specific inflammation [ 179 , 180 ]. Since naked siRNAs are negatively charged hydrophilic molecules, they cannot spontaneously cross cell membranes. Consequently, different delivery strategies are currently under study, such as chemical modification, encapsulation into lipid or polymeric carriers or conjugation with organic molecules (polymers, peptides, lipids, antibodies, small molecules [ 181 ], for efficient targeting [ 182 , 183 ]). Chemical modifications include the insertion of a phosphorothioate at 3’ end to reduce exonuclease degradation [ 184 ], the introduction of 2’ O-methyl group to obtain longer half-life in plasma [ 185 ] and the modification by 2,4-dinitrophenol to favour membrane permeability [ 186 ]. Nevertheless, the degradation of modified siRNAs often elicits cytotoxic effects; therefore, it is preferable to design ad hoc nanocarriers.

Different cationic lipid nanoparticles, such as liposomes, micelles and solid lipid nanoparticles [ 183 ], have been exploited for siRNA loading. Cationic liposomes interact with negatively charged nucleic acids, which can be easily transfected by simple electrostatic interactions [ 187 , 188 ]. They can be constituted by 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and N-{1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl sulphate (DOTMA) [ 189 ]. A theranostic agent consisting of an anticancer survivin siRNA entrapped in PEGylated liposomes has been developed to achieve simultaneous localisation inside tumour cells by means of entrapped MR agents and fluorophores and reduction of proliferation in vivo [ 190 ].

Neutral liposomes based on 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) have shown high efficacy in mice models of ovarian carcinoma and colorectal cancer [ 191 , 192 ]. A phase I clinical trial is currently recruiting patients for evaluating the safety of siRNA-EphA2-DOPC when administered to patients with advanced and recurrent cancer [ 193 ].

Stable nucleic acid lipid particles (SNALPs) have been evaluated in non-human primates [ 194 ]. SiRNAs have been encapsulated in a mixture of cationic lipids coated with a shell of polyethylene glycol (PEG) [ 195 ]. SNALPs entered a phase I clinical trial in patients affected by advanced solid tumours with liver involvement [ 196 ] and a phase I/II trial for treating neuroendocrine tumours and adrenocortical carcinoma patients refractory to standard therapy [ 197 ].

SiRNAs can be condensed in cationic polymers such as chitosan, cyclodextrin and polyethylenimine (PEI). Chitosan is a natural polysaccharide that, due to its cationic charge, has been exploited as carrier for nucleic acids in vitro and in vivo [ 198 ]. Specifically, a targeted siRNA has been delivered in mice xenografts of breast cancer [ 199 ]. Cyclodextrin polymers coated with PEG, conjugated with human transferrin and carrying a siRNA called CALAA-01, inhibit tumour growth by reducing the expression of M2 subunit of ribonucleotide reductase (R2), and have entered a phase I clinical trial [ 200 ]. PEI is able to form small cationic nanoparticles containing siRNAs and it has been exploited as antitumoural, upon loading with HER-2 receptor-specific siRNA [ 201 ]. A phase II clinical trial is presently starting to evaluate siG12D LODER directed to mutated KRAS oncogene and encapsulated into a biodegradable polymeric matrix for locally treating advanced pancreatic cancer patients in combination with chemotherapy [ 202 ].

SiRNAs may be conjugated to peptides, antibodies and aptamers in order to improve their stability during circulation and to enhance cellular uptake [ 203 ]. A success is represented by siRNAs targeting PSMA, overexpressed in this type of cancer [ 204 ].

The introduction of nanocarriers has largely improved siRNAs stability, pharmacokinetics and biodistribution properties, and the targeting specificity [ 205 , 206 ]. Smart nanomaterials responsive to external (i.e., magnetic field, ultrasounds) and tumour-specific stimuli (i.e., acidic pH, redox conditions) are currently under the development for controlled release and reduction of undesired negative effects [ 207 , 208 ]. Nanocarriers delivering siRNAs undergo a series of pH variations from blood circulation to intracellular environment and, for this reason, many pH responsive materials have been designed to favour cargo release under specific pH conditions [ 209 ]. Poly(allylamine) phosphate nanocarriers, stable at physiological pH, have been developed to release siRNAs in the cytoplasm after disassembly at low endosomal pH [ 210 ].

Although there have been many successes, some questions remain open and make the clinical translation of the siRNA-based approach very challenging, such as the correct doses to be delivered to patients and the many variabilities observed between individuals and different stages of disease. Further research towards controlled release to reach only specific targets, and the set-up of the best personalised therapy for cancer patients will be necessary in the near future.

Thermal ablation and magnetic hyperthermia

Thermal ablation of tumours includes a series of techniques that exploit heat (hyperthermia) or cold (hypothermia) to destroy neoplastic tissues [ 13 ]. It is known that cell necrosis occurs at temperatures lower than -40°C or higher than 60°C. Long exposures to temperatures between 41°C and 55°C are also effective for tumour cell damage. Moreover, it has been shown that cancer cells are more sensitive to high temperatures than healthy ones [ 211 ].

Hypothermic ablation is due to the formation of ice crystals upon cooling, which destroy cell membranes and finally kill cells. Argon gas is the preferred cooling agent because it can cool down the surrounding tissues to -160°C. Also, gases at their critical point, such as nitrogen, can be exploited since they have a higher heat capacity than argon. However, the technology to control and direct them is not well developed yet [ 10 ].

Hyperthermic ablation currently comprises radiofrequency (RF), microwave and laser ablation [ 10 ].

RF ablation is the most used in clinics, because it is effective and safe [ 212 ]. An alternated current of RF waves is applied to a target zone by an insulated electrode tip, while a second electrode, needed to close the circuit, is placed on the skin surface [ 10 ]. The interaction with the current causes the oscillation of ions in the extracellular fluid, which, in turns, produces heat. The more conductive the medium, the more effective the process. For this reason, RF ablation works very well in the liver and in other areas with a high content of water and ions, whereas it has a poor effect in lungs [ 10 ]. Moreover, the efficiency of the treatment decreases with the size of the lesion, giving the best results for areas not larger than 3 cm 2 [ 213 , 214 ].

Microwave ablation is based on the electromagnetic interaction between microwaves and the polar molecules in tissues, like water, that causes their oscillation and the consequent increase in temperature. Unlike the electrical current in RF ablation, microwaves can propagate through any kind of tissue [ 215 , 216 ], and this allows high temperatures to be reached in a short amount of time, to have a deeper penetration and to treat larger areas of tumours [ 217 ].

Laser therapy exploits the properties of laser beams of being very narrow and extremely focused at a specific wavelength. This makes the treatment very powerful and precise, thus a promising alternative to conventional surgery [ 218 ]. The absorption of the light emitted by the laser results in the heating and subsequent damage of the treated area [ 219 ]. Depending on the specific application, different kinds of lasers can be used. Neodymium:yttrium-aluminium-garnet (Nd:YAG) lasers (wavelength of 1064 nm) and diode lasers (wavelength of 800–900 nm) are used to treat internal organs, since they have a penetration depth up to 10 cm [ 218 ]. Conversely, CO 2 lasers (10,600 nm), with a penetration depth of 10 μm up to 1 mm maximum are used for superficial treatments. Laser therapy is receiving a lot of attention in research because of its advantages compared to other ablation techniques, such as a higher efficacy, safety and precision, and a shorter treatment session needed to achieve the same results [ 220 , 221 ]. Moreover, the fibres to transmit laser light are compatible with MRI, allowing for a precise measure of the temperature and the thermal dose [ 222 ]. However, there are still some limitations to overcome, such as the need of a very skilled operator to place the fibre in the correct position [ 218 ].

Finally, a new way to heat tumour tissues, currently under study, is through magnetic hyperthermia. This technique exploits superparamagnetic or ferromagnetic nanoparticles that can generate heat after stimulation with an alternating magnetic field. The most studied systems in nanomedicine are SPIONs [ 11 ]. The production of heat, in this case, is due to the alignment of magnetic domains in the particles when the magnetic field is applied, and the subsequent relaxation processes (Brownian and/or Neel relaxations) during which heat is released, when the magnetic field is removed and the magnetisation of the particles reverts to zero [ 223 ]. Magnetic hyperthermia can reach any area of the body and SPIONs can also act as MRI contrast agents to follow their correct localisation before the stimulation. The particles can be coated with biocompatible polymers and/or lipid and functionalized with specific ligands to impart targeting properties [ 224 ]. As already mentioned, until now, just a formulation of 15-nm iron oxide nanoparticles coated with aminosilane (Nanotherm) obtained approval for the treatment of glioblastoma [ 31 ]. SPIONs have also been successfully encapsulated in lipid nanocarriers together with a chemotherapeutic agent to combine chemotherapy and hyperthermia [ 49 , 50 ].

Recent innovations in cancer therapy: Radiomics and pathomics

Efficient cancer therapy currently relies on surgery and, in approximately 50% of patients, on radiotherapy, that can be delivered by using an external beam source or by inserting locally a radioactive source (in this case, the approach is named brachytherapy), thus obtaining focused irradiation. Currently, localisation of the beam is facilitated by image-guided radiotherapy (IGRT), where images of the patient are acquired during the treatment allowing the best amount of radiation to be set. Thanks to the introduction of intensity-modulated radiotherapy (IMRT), radiation fields of different intensities can be created, helping to reduce doses received by healthy tissues and thus limiting adverse side effects. Finally, by means of stereotactic ablative radiotherapy (SABR), it has become feasible to convey an ablative dose of radiation only to a small target volume, significantly reducing undesired toxicity [ 225 ].

Unfortunately, radioresistance can arise during treatment, lowering its efficacy. This has been linked to mitochondrial defects; thus, targeting specific functions have proven to be helpful in restoring anti-cancer effects [ 226 ]. A recent study has shown, for example, that radioresistance in an oesophageal adenocarcinoma model is linked to an abnormal structure and size of mitochondria, and the measurement of the energy metabolism in patients has allowed discrimination between treatment resistant and sensitive patients [ 227 ]. Targeting mitochondria with small molecules acting as radiosensitizers is being investigated for gastrointestinal cancer therapy [ 228 ].

Cancer is a complex disease and its successful treatment requires huge efforts in order to merge the plethora of information acquired during diagnostic and therapeutic procedures. The ability to link the data collected from medical images and molecular investigations has allowed an overview to be obtained of the whole tridimensional volume of the tumour by non-invasive imaging techniques. This matches with the main aim of precision medicine, which is to minimise therapy-related side effects, while optimising its efficacy to achieve the best individualised therapy [ 229 ].

Radiomics and pathomics are two promising and innovative fields based on accumulating quantitative image features from radiology and pathology screenings as therapeutic and prognostic indicators of disease outcome [ 12 , 13 , 230 ]. Many artificial intelligence technologies, such as machine learning application, have been introduced to manage and elaborate the massive amount of collected datasets and to accurately predict the treatment efficacy, the clinical outcome and the disease recurrence. Prediction of the treatment response can help in finding an ad hoc adaptation for the best prognosis and outcome. Nowadays, personalised medicine requires an integrated interpretation of the results obtained by multiple diagnostic approaches, and biomedical images are crucial to provide real-time monitoring of disease progression, being strictly correlated to cancer molecular characterisation.

Radiomics is intended as the high throughput quantification of tumour properties obtained from the analysis of medical images [ 14 , 15 , 231 ]. Pathomics, on the other side, relies on generation and characterisation of high-resolution tissue images [ 16 , 232 , 233 ]. Many studies are focusing on the development of new techniques for image analysis in order to extrapolate information by quantification and disease characterisation [ 234 , 235 ]. Flexible databases are required to manage big volumes of data coming from gene expression, histology, 3D tissue reconstruction (MRI) and metabolic features (positron emission tomography, PET) in order to identify disease phenotypes [ 236 , 237 ].

Currently, there is an urgent need to define univocal data acquisition guidelines. Some initiatives to establish standardised procedures and facilitate clinical translation have been already undertaken, such as quantitative imaging network [ 238 ] or the German National Cohort Consortium [ 239 ]. Precise description of the parameters required for image acquisition and for the creation and use of computational and statistical methods are necessary to set robust protocols for the generation of models in radiation therapy. According to the US National Library of Medicine, approximately 50 clinical trials involving radiomics are currently recruiting patients, and a few have already been completed [ 240 ].

Conclusions and future perspectives

In recent years, research into cancer medicine has taken remarkable steps towards more effective, precise and less invasive cancer treatments ( Figure 1 ). While nanomedicine, combined with targeted therapy, helped improving the biodistribution of new or already tested chemotherapeutic agents around the specific tissue to be treated, other strategies, such as gene therapy, siRNAs delivery, immunotherapy and antioxidant molecules, offer new possibilities to cancer patients. On the other hand, thermal ablation and magnetic hyperthermia are promising alternatives to tumour resection. Finally, radiomics and pathomics approaches help the management of big data sets from cancer patients to improve prognosis and outcome.

At the moment, the most frequent entries concerning cancer therapies in the database of clinical trials ( www.clinicaltrials.gov ) involve the terms targeted therapy, immunotherapy and gene therapy, highlighting that these are the most popular methodologies under investigation, especially because, as already mentioned before, they have been shown to be very promising and effective ( Figure 2A ). However, Figure 2B shows that the clinical trials started in the past decade on different therapies mentioned in this review (except for liposomes-based therapies) have increased in number, showing how the interest on these new approaches is quickly growing in order to replace and/or improve conventional therapies. In particular, radiomics, immunotherapy and exosomes are the entries whose number has increased the most in the last 10 years.

The current scenario for cancer research is wide, offering many possibilities for the constant improvement of treatment, considering not only patient recovery but also caring for their well-being during therapy. As summarised in Table 1 , these new approaches offer many advantages compared to conventional therapies. However, some disadvantages still have to be overcome to improve their performances. Much progress has been made, but many others are likely to come in the near future, producing more and more ad hoc personalised therapies.

Conflicts of interest

The authors declare that they have no conflict of interest.

Funding declaration

This work was partially supported by the Fondazione CaRiPLo, grant no. 2018-0156 (Nanotechnological countermeasures against Oxidative stress in muscle cells Exposed to Microgravity—NOEMI) and by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement N°709613, SLaMM).

Authors’ contributions

Carlotta Pucci and Chiara Martinelli contributed equally to this work.

Home > AACR Cancer Progress Report > AACR Cancer Progress Report 2023: Contents > Advancing the Frontiers of Cancer Science and Medicine

• Advancing the Frontiers of Cancer Science and Medicine

In this section, you will learn:

• Researchers are harnessing the knowledge of the cellular and molecular underpinnings of cancer initiation and progression to develop safer and more effective treatments for cancer.
• Advances in novel and innovative approaches to surgery, radiotherapy, chemotherapy, molecularly targeted therapy, and immunotherapy—the five pillars of cancer treatment—are saving and improving lives.
• From August 1, 2022, to July 31, 2023, FDA has approved 14 new anticancer therapeutics and two new imaging agents and has expanded the use of 12 previously approved anticancer therapeutics to treat additional cancer types.
• Included in the FDA approvals are the first antibody–drug conjugate for the treatment of ovarian cancer, several new molecularly targeted therapeutics and immunotherapeutics to treat rare cancers including blood cancers, two new immune checkpoint inhibitors, and a first of a kind gene therapy to treat bladder cancer.
• While these exciting new advances have the potential to transform patient care, much work is needed to ensure equitable access to these treatments for all populations.

Clinical Research

Progress across the clinical cancer care continuum, advances in cancer treatment with surgery, improvements in radiation-based approaches to cancer care, advances in treatment with cytotoxic chemotherapy, advances in treatment with molecularly targeted therapy.

Progress across the continuum of cancer research and patient care improves survival and quality of life for people around the world. In the United States, the annual decline in overall cancer death rate among men, women, children, and adolescents and young adults has accelerated over the past two decades (see Cancer in 2023 ) ( 325 ) Cronin KA, et al. (2022) Cancer, 128: 4251. [LINK NOT AVAILABLE] . This progress is driven by the dedicated efforts of individuals working throughout the cycle of medical research (see Figure 4 and Sidebar 25 ).

The rapid pace of progress against cancer is attributable in part to the new and effective treatments that are available today, thanks to the discoveries made through decades of research in basic and translational sciences. These discoveries have deepened our understanding of the cellular and molecular underpinnings of cancer initiation and progression and led to the identification of a range of molecular targets that drive cancer (see Understanding the Path to Cancer Development ). After a potential therapeutic target is identified, it takes many more years of preclinical research before a candidate therapeutic is developed and ready for testing in clinical trials (see Sidebar 26 ).

Clinical trials evaluate the safety and efficacy of candidate agents before a preventive intervention or therapeutic can be approved by FDA and used as part of patient care. All clinical trials are critically reviewed and approved by institutional review boards before they can begin and are monitored throughout their duration. There are several types of cancer clinical trials, including prevention trials, screening trials, treatment trials, and supportive or palliative care trials, each designed to answer different research questions (see Sidebar 27 ). Clinical studies in which participants are randomly assigned to receive experimental treatment or standard of care treatment are called randomized clinical trials and are considered the most rigorous.

Clinical trials that test candidate therapeutics for patients with cancer have traditionally been done in three successive phases (see Figure 13 ). Observations made during the real-world use of a drug after it is approved by FDA can also be utilized to further enhance the use of that drug. The multiphase clinical testing process requires many patients, takes years to complete, and has a high rate of failure, making it extremely costly and one of the main barriers to rapid translation of scientific knowledge into clinical advances ( 326 ) Arfe A, et al. (2023) J Natl Cancer Inst, 115:917 [LINK NOT AVAILABLE] ( 327 ) Shadbolt C, et al. (2023) JAMA Netw Open, 6: e2250996. [LINK NOT AVAILABLE] . Identifying and implementing more efficient clinical development strategies are an area of extensive investigation for all stakeholders in medical research (see Sidebar 1 ).

Advances in the understanding of cancer biology have enabled researchers from academia and the pharmaceutical industry to develop new approaches to designing and conducting clinical trials. Among the new concepts and designs for clinical trials that have emerged in recent years are the adaptive, main protocol, and platform trials designs ( 329 ) Li A, et al. (2020) Cancer, 126: 4838. [LINK NOT AVAILABLE] . These designs allow researchers to modify aspects of the trial design, if needed, by leveraging the accumulating data, thereby increasing the efficiency of the clinical research process. Main protocol, also known as master protocol design, and platform design streamline clinical development and allow the evaluation of multiple new agents by matching the right therapeutics with the right patients earlier, reducing the number of patients who need to be enrolled in the trial, and decreasing the length of time it takes for a new anticancer therapeutic to be tested and made available to patients.

Master protocol can answer multiple clinical questions within a single trial ( 329 ) Li A, et al. (2020) Cancer, 126: 4838. [LINK NOT AVAILABLE] . The emergence of this clinical trial design has largely been driven by accumulating knowledge of the genetic mutations that underpin cancer initiation and growth. As one example, I-SPY 2 is one of the longest-running clinical trials that uses a master protocol which provides the regulatory framework to study multiple treatments for breast cancer within a single study ( 330 ) Quantum Leap Healthcare Collaborative. The I-SPY Trials. Accessed: July 31, 2023. . The platform design of the I-SPY 2 trial allows new treatments to enter and leave the study with a greater efficiency than traditional clinical trials. The study has led to the FDA approval of several breast cancer treatments, including the molecularly targeted therapeutic neratinib (Nerlynx) ( 331 ) Wang H, et al. (2019) Curr Breast Cancer Rep, 11: 303. [LINK NOT AVAILABLE] .

Basket trials are another example of genetic mutation–based master protocol design in clinical trials (see Figure 14 ). These trials allow researchers to test one anticancer therapeutic on a group of patients who all have the same type of genetic mutation, regardless of the anatomic site of the original cancer. As one example, the combination of molecularly targeted therapeutics dabrafenib and trametinib was shown to work against an array of cancer types characterized by a specific genetic feature, or biomarker, called the BRAF V600E mutation, in two recent basket trials including the NCI MATCH study (see Sidebar 9 ) ( 109 ) O’Dwyer PJ, et al. (2023) Nat Med, 29: 1349. [LINK NOT AVAILABLE] . Based on the data from these trials, the combination treatment received FDA approval in June 2022 and is now benefiting many patients with cancer ( 1 ) American Association for Cancer Research. AACR Cancer Progress Report 2022. Accessed: July 5, 2023. . Based on a recent analysis, the use of novel trial designs in clinical cancer research has more than tripled, worldwide, over the past decade ( 332 ) IQVIA. Global Oncology Trends 2023. Accessed: July 5, 2023. .

As our understanding of cancer biology continues to evolve and we uncover some of the most elusive questions in cancer medicine (see C ancer Development: Integrating Knowledge ) clinical trial designs will need to evolve as well. Additionally, the design and conduct of clinical cancer research need to keep pace with the new wave of technological advances. Novel designs that integrate emerging approaches such as comprehensive tumor profiling (e.g., of genome, transcriptome, proteome, microbiome, and metabolome, among others), artificial intelligence and machine learning, real-world evidence and data, and leverage inputs from patient advocacy communities and social media platforms will be pivotal to advancing the frontier of cancer clinical trials ( 333 ) Subbiah V (2023) Nat Med, 29: 49. [LINK NOT AVAILABLE] .

Two of the most pressing challenges that need to be overcome urgently are low participation in cancer clinical trials and a lack of sociodemographic diversity among those who do participate (see Sidebar 28 ). Low participation in clinical trials means that many trials fail to enroll enough participants to draw meaningful conclusions about the effectiveness of the anticancer therapeutic being tested. Lack of diversity in clinical studies means that the trial participant population does not match the actual demographics of the cancer burden under study ( 334 ) In: Bibbins-Domingo K, Helman A, editors. Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups. Washington (DC)2022. [LINK NOT AVAILABLE] . Underrepresentation in clinical trials compromises the applicability of such research findings to the entire U.S. patient population.

Understanding and eliminating barriers to clinical trial participation for all segments of the population is vital if we are to accelerate the pace of progress against cancer for everyone. Numerous studies have investigated the existing barriers that limit participation of racial and ethnic minorities and other medically underserved populations in cancer clinical trials. These studies have identified a range of factors such as lack of awareness of clinical trials, financial challenges, limited health literacy, inadequate or complete lack of insurance, medical distrust, implicit biases among health care providers, lack of trial availability, and narrow eligibility criteria, among others ( 13 ) American Association for Cancer Research. AACR Cancer Disparities Progress Report 2022. Accessed: June 30, 2023. . These barriers operate at individual, systemic, and societal levels ( 340 ) Kahn JM, et al. (2022) Cancer, 128: 216. [LINK NOT AVAILABLE] .

Increased knowledge of the barriers to clinical trial accrual is helping researchers, regulators, and policymakers design and implement evidence-based adaptations that can broaden participant access and promote accrual to clinical research. Such interventions focus on addressing social determinants of health (see Figure 2 ), and include decentralizing many of the trial activities to ease patient participation, expanding eligibility criteria, improving the efficiency of data collection, including patient reported outcomes (PRO), and enhancing community outreach and patient navigation efforts to raise awareness of trials. One critical area of focus for all stakeholders in medical research is fostering greater diversity, equity, and inclusion within the clinical research workforce so the workforce will resemble the patient populations it serves.

U.S. lawmakers and FDA are working on legislation and guidelines intended to increase the diversity of clinical trial participants (see D iversifying and Decentralizing Trials ). These include a diversity action plan which would require researchers and funders of clinical trials to submit concrete goals and needed steps for enrolling specific demographic groups in pivotal studies of new drugs ( 341 ) U.S. Food and Drug Administration. Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials; Draft Guidance for Industry; Availability. Accessed: July 5, 2023. . COVID-19, despite its adverse effects on all aspects of cancer research and patient care, enabled researchers to decentralize clinical trial designs, so that lifesaving therapeutics could be brought quickly to as many patients as possible ( 9 ) American Association for Cancer Research. AACR Report on the Impact of COVID-19 on Cancer Research and Patient Care. Accessed: June 30, 2022. . Adaptations implemented by NCI and FDA during the pandemic, including consenting patients remotely, permitting telehealth for routine clinical assessments (see Sidebar 29 ), delivering experimental drugs to patients, and allowing the use of local laboratory or imaging facilities accessible to patients have offered a blueprint of success to further revise and reform clinical trials and the drug approval process for the benefit of all patients with cancer.

Research discoveries made as a result of innovative cancer science are continually being translated into new medical products for cancer prevention, detection, diagnosis, treatment, and survivorship. The approval of new medical products, including new anticancer treatments, is not the end of a linear research process. Rather, it is an integral part of the medical research cycle (see Figure 4 ) because observations made during the routine use of new medical products can be used to accelerate the pace at which similar products are developed and to stimulate the development of new, more effective products.

New FDA-approved medical products are traditionally utilized alongside treatments already in use, including surgery, radiotherapy, and cytotoxic chemotherapy, which continue to be the mainstays of clinical cancer care (see Figure 15 ). Researchers are also evaluating new ways to refine the use of surgery, radiotherapy, and existing cytotoxic chemotherapeutics to improve survival and quality of life for patients. As one example, a recent clinical trial showed that for patients with early-stage prostate cancer, active monitoring of their disease is a safe alternative to receiving immediate surgery or radiotherapy ( 346 ) Hamdy FC, et al. (2023) N Engl J Med, 388: 1547. [LINK NOT AVAILABLE] . In most cases, prostate cancer grows slowly. Therefore, the study directly compared the long-term outcomes of the three approaches, prostate removal surgery, radiotherapy, or active monitoring and found that there was no difference in prostate cancer mortality at the 15-year follow-up between the three groups. These data provide hope for patients with prostate cancer who opt for active monitoring to avoid treatment-related adverse effects, such as sexual and incontinence problems.

The following sections focus on the recent advances across the five pillars of cancer treatment including the 14 new anticancer therapeutics approved by the FDA in the 12 months spanning this report, August 1, 2022, to July 31, 2023 (see Table 3 and Supplemental Table 2 ). Also highlighted are the 12 previously approved anticancer therapeutics that received FDA approval for treating additional types of cancer in that period.

Not discussed are FDA approvals that expand the use of an anticancer therapeutic previously approved for a given cancer type to include treatment with that therapeutic at different timepoints during the course of clinical care or treatment of a different subtype of the same cancer. For example, the August 2022 FDA approval expanded the use of fam-trastuzumab-deruxtecan-nxki (Enhertu), for the treatment of patients with metastatic HER2-low breast cancer that is not removable by surgery. This expansion occurred nearly three years after the molecularly targeted therapeutic was first approved for treating metastatic HER2-positive breast cancer and was based on results from a phase III clinical trial. The study showed that patients with metastatic breast cancer who were treated with fam-trastuzumab-deruxtecan-nxki lived nearly twice as long without their cancer progressing and lived six months longer overall than those treated with standard chemotherapy ( 352 ) Modi S, et al. (2022) N Engl J Med, 387: 9. [LINK NOT AVAILABLE] . Fam-trastuzumab-deruxtecan-nxki is the first treatment approved for patients with HER2-low breast cancer subtype, a newly defined subset of HER2-negative breast cancer.

New medical products used across the continuum of clinical cancer care transform lives by improving survival and quality of life. However, not all patients receive the standard of care recommended for the type of cancer with which they have been diagnosed and the stage of cancer at the time of diagnosis (see Sidebar 30 ). Thus, it is imperative that all stakeholders committed to driving progress against cancer work together to address the challenge of disparities in cancer treatment because these can be associated with adverse differences in survival. Recent studies have shown that disparities in survival for prostate cancer or multiple myeloma between Black patients and White patients can be eliminated when both population groups have equivalent access to care and to standard treatments ( 13 ) American Association for Cancer Research. AACR Cancer Disparities Progress Report 2022. Accessed: June 30, 2023. .

For many years, surgery was the only pillar of cancer treatment (see Figure 15 ). Today, it remains the foundation of curative treatment for many patients. Surgery is used in several ways during the care of a patient with cancer (see Sidebar 31 ).

Sometimes, additional therapy is given before, after, or around the time of surgery based on specifics of a patient’s situation (see Sidebar 32 ). Researchers have found that this approach not only improves the surgeon’s ability to remove the tumor (for example by shrinking the tumor when given before the surgery), but also increases the patient’s overall survival and/or quality of life ( 359 ) Burotto M, et al. (2019) Semin Oncol, 46: 83. [LINK NOT AVAILABLE] .

Improving Quality of Life After a Cancer Surgery

Despite the immense benefits of surgery for the treatment of cancer, complications are common and can negatively affect patient quality of life. Enhanced recovery after surgery (ERAS) programs are emerging as one approach to address this issue. These comprehensive programs focus on optimizing patient care before, during, and after surgery using strategies that ensure the patient is as physically and emotionally fit for surgery as possible; alleviate the stress of surgery; promote recovery; and reduce the time before patients with cancer can begin adjuvant treatment. Providing patients with an individualized plan that includes exercise, nutrition, stress reduction, and smoking cessation to optimize their physical fitness before surgery is one strategy included in some ERAS programs ( 360 ) Gustafsson UO, et al. (2019) World J Surg, 43: 659. [LINK NOT AVAILABLE] ( 361 ) Santa Mina D, et al. (2017) PM R, 9: S305. [LINK NOT AVAILABLE] . The components of ERAS programs can vary depending on the type of surgery being performed and the center at which the surgery is being performed, but overall, these programs have been promising.

One study found that among patients undergoing surgery for tumors that have metastasized to the spine, those who participated in an ERAS program had reduced blood loss, shorter hospitalization, and significant reduction in opioid pain reliever utilization compared to those who did not participate ( 362 ) Chakravarthy VB, et al. (2022) Cancer, 128: 4109. [LINK NOT AVAILABLE] . Another study showed that among patients undergoing surgery for colorectal cancer, those who participated in an individualized plan that included exercise, nutritional intervention, and psychological support had fewer medical complications and better recovery postsurgery than those who did not participate in such programs ( 363 ) Molenaar CJL, et al. (2023) JAMA Surg, 158: 572. [LINK NOT AVAILABLE] .

Other approaches to reducing the complications during and after surgery and improving quality of life postprocedure are to perform less extensive and minimally invasive surgeries, such as robotic surgeries or to identify a subset of patients who could skip surgery altogether.

As one example, data from a recent clinical trial showed that for certain patients with early-stage non–small cell lung cancer (NSCLC), surgical removal of only part of the affected lobe of lung is an effective treatment option ( 364 ) Altorki N, et al. (2023) N Engl J Med, 388: 489. [LINK NOT AVAILABLE] . The study, which compared the outcomes of patients who had their entire lobes removed to those who had only the tumor-affected regions removed, showed that the 5-year overall survival was similar in the two groups. While the study participants represent only a select subgroup of patients with lung cancer, these data are important considering that removal of less lung tissue can preserve lung function, especially for older adults and those with compromised lung capacity, such as patients with a prior lung cancer.

Studies have shown that less invasive surgeries may benefit patients since they can minimize postprocedural complications without compromising and sometimes improving long-term outcomes ( 365 ) Topal H, et al. (2022) JAMA Netw Open, 5: e2248147. [LINK NOT AVAILABLE] ( 366 ) Son SY, et al. (2022) JAMA Surg, 157: 879. [LINK NOT AVAILABLE] ( 367 ) Di Benedetto F, et al. (2023) JAMA Surg, 158: 46. [LINK NOT AVAILABLE] . As one example, in a recent clinical trial, patients with locally advanced stomach cancer who underwent a minimally invasive procedure had significantly lower long-term complications after surgery, but similar 5-year overall and relapse-free survival rates compared to those who had open surgeries ( 366 ) Son SY, et al. (2022) JAMA Surg, 157: 879. [LINK NOT AVAILABLE] . Additionally, two retrospective analyses showed improved disease-free and overall survival for patients with pancreatic cancer and reduced morbidity during surgery for patients with liver cancer who underwent minimally invasive surgeries compared to those who received open surgeries ( 365 ) Topal H, et al. (2022) JAMA Netw Open, 5: e2248147. [LINK NOT AVAILABLE] ( 367 ) Di Benedetto F, et al. (2023) JAMA Surg, 158: 46. [LINK NOT AVAILABLE] . Yet another report from an early-stage clinical trial showed that a selected subset of patients with breast cancer who responded remarkably well to neoadjuvant chemotherapy could potentially forgo surgery without risking tumor recurrence ( 368 ) Kuerer HM, et al. (2022) Lancet Oncol, 23: 1517. [LINK NOT AVAILABLE] .

Recent studies have also identified subsets of patients who could skip surgery altogether without compromising outcomes. In a clinical trial, women who had early-stage ( 368 ) Kuerer HM, et al. (2022) Lancet Oncol, 23: 1517. [LINK NOT AVAILABLE] reast cancer with defined clinical characteristics had equally good overall survival whether they received radiotherapy delivered to the lymph nodes in their underarms (axillary radiotherapy), or an invasive surgical procedure to remove these lymph nodes (axillary lymph node dissection) ( 369 ) Bartels SAL, et al. (2023) J Clin Oncol, 41: 2159. [LINK NOT AVAILABLE] . Notably, axillary lymph node dissection is associated with a significantly higher rate of morbidity, particularly lymphedema, which causes swelling in the arms that can cause pain and problems in functioning. These risks are drastically reduced if radiotherapy is given instead and suggests radiation rather than surgery should be the preferred approach in these patients.

While less invasive approaches to surgery such as those described above are promising, before they can become standard of care, it is vital that they are shown in rigorous, well-designed, larger clinical trials to have no adverse effect on long-term patient survival.

Visualizing Lung Cancers More Precisely During Surgery

Lung cancer is the leading cause of cancer deaths in the United States with an estimated 127,070 deaths predicted in 2023 ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . While surgery is the standard treatment and provides the best chance to cure early-stage lung cancer, up to 55 percent of people with lung cancer who undergo surgery with curative intent have a recurrence ( 370 ) Uramoto H, et al. (2014) Transl Lung Cancer Res, 3: 242. [LINK NOT AVAILABLE] . Therefore, it is vital that the entire tumor is removed during surgery. Surgeons rely on either imaging tumors before surgery, visually inspecting tumors under normal white light during surgery, or examining tumors by touch to identify cancerous tissue. Unfortunately, some lung lesions can be difficult to visualize, particularly if they are small, beneath the surface of the lung, or a type of lesion characterized by increased opacity of the lung called ground glass opacity, which is being increasingly diagnosed as the rates of lung cancer screenings rise ( 371 ) Migliore M, et al. (2018) Ann Transl Med, 6: 90. [LINK NOT AVAILABLE] ( 372 ) Huang C, et al. (2019) J Cancer, 10: 6888. [LINK NOT AVAILABLE] .

In December 2022, the FDA approved pafolacianine (Cytalux), a folate receptor–targeted fluorescent agent, as the first and only targeted molecular imaging agent that illuminates lung cancers and enhances surgeons’ ability to see cancer in real time as they operate. Molecular imaging using pafolacianine during surgery enables the detection of lung lesions that may have otherwise been missed. Pafolacianine was previously approved to assist surgeons in visualizing hard to detect lesions in adult patients with ovarian cancer during surgery ( 1 ) American Association for Cancer Research. AACR Cancer Progress Report 2022. Accessed: July 5, 2023. . Pafolacianine binds to folate receptors, a protein that is commonly found on the surface of many cancers and illuminates tumor cells under near-infrared light. The agent is administered via intravenous infusion within 24 hours before surgery and assists surgeons in visually identifying additional malignant tissue to be removed during the procedure.

The approval in lung cancer was based on a clinical trial that evaluated the utility of pafolacianine in visualizing tumors in the lungs that may otherwise be undetected with conventional visualization under white light ( 373 ) Sarkaria IS, et al. (2023) J Thorac Cardiovasc Surg. [LINK NOT AVAILABLE] . Molecular imaging using pafolacianine during surgery identified in 19 percent of patients primary lung nodules that surgeons could not find using white light and palpation; additionally, pafolacianine revealed in eight percent of patients additional lesions that were completely missed using white light. The expanded approval of pafolacianine represents a significant advancement in the treatment of lung cancer by enhancing detection of lung tumors during surgery, improving the ability to remove them completely, and reducing the probability of leaving behind cancerous tissue.

Radiotherapy is the use of high-energy rays (e.g., gamma rays and X-rays) or particles (e.g., electrons, protons, and carbon nuclei) to control or eradicate cancer. Discovery of X-rays in 1895 allowed visualization of internal organs at low doses, and the effective use of X-rays at high doses to treat a breast cancer patient a year later established radiotherapy as the second pillar of cancer treatment (see Figure 15 ). Radiotherapy plays a central role in the management of cancer and works primarily by damaging DNA, leading to cancer cell death. The use of radiotherapy in treatment and management of cancer continues to increase, as indicated by a 16.4 percent increase in radiation facilities across the United States between 2005 and 2020 ( 374 ) Maroongroge S, et al. (2022) Int J Radiat Oncol Biol Phys, 112: 600. [LINK NOT AVAILABLE] .

There are many types and uses of radiotherapy (see Sidebar 33 ). However, it is important to note that radiotherapy may also have harmful side effects, partly because of the radiation-induced damage to healthy cells surrounding the tumor tissue ( 375 ) Wang K, et al. (2021) CA Cancer J Clin, 71: 437. [LINK NOT AVAILABLE] .

Researchers are continuously working on making radiotherapy safer and more effective and identifying when radiotherapy can be avoided without affecting the chances of survival for patients. As one example, a recent clinical trial showed that older adult patients with small, early-stage breast cancer may forgo radiation after breast conserving surgery without compromising their overall survival ( 376 ) Kunkler IH, et al. (2023) N Engl J Med, 388: 585. [LINK NOT AVAILABLE] . Traditionally, in these patients, surgery has been followed with radiotherapy to reduce the risk of cancer recurrence. However, radiotherapy can lead to a range of potential side effects including pain, minor risks of organ damage and secondary cancer, as well as time and financial losses. Adverse effects are especially challenging for older adults, many of whom have other comorbidities. The new evidence provides these patients with the option for a less aggressive course of action.

Another clinical trial showed that radiation therapy before initial surgery may not be needed for patients with locally advanced rectal cancer that has spread locally within the rectum but not to other organs ( 377 ) Schrag D, et al. (2023) N Engl J Med, 389: 322. [LINK NOT AVAILABLE] . Traditionally, these patients receive radiation combined with chemotherapy, also known as chemoradiotherapy, before surgical removal of their tumors. Chemoradiotherapy shrinks the tumor making it easier to remove and helping to prevent recurrence. Data from the recent clinical trial showed that chemotherapy alone before surgery was just as effective as chemoradiotherapy at keeping the cancer at bay ( 377 ) Schrag D, et al. (2023) N Engl J Med, 389: 322. [LINK NOT AVAILABLE] .

Researchers are also designing novel radiotherapeutics, to be used alone or in combination with other treatments, to target more cancer types and benefit more patients. Additionally, technological innovations, such as the development of advanced imaging and sophisticated computer analytic programs assisted by AI, are helping optimize the delivery of the radiation to the tumor while minimizing exposure to normal tissues ( 378 ) Santoro M, et al. (2022) Applied Sciences, 12: 3223. [LINK NOT AVAILABLE] . As one example, Magnetic Resonance Imaging (MRI)-guided radiotherapy (MRgRT) is a novel technology with the potential to transform radiotherapy for many patients including those with prostate cancer ( 379 ) Ng J, et al. (2023) Front Oncol, 13: 1117874. [LINK NOT AVAILABLE] . MRgRT provides the ability to image tumors and internal organs with MRI and adapt the radiotherapy plan in real-time while the patient is undergoing the procedure. Unlike traditional radiotherapy, MRgRT allows monitoring of changes in tumor size and positional changes of internal organs during each treatment to achieve a more accurate delivery of the radiation dose. This is particularly critical for rapidly changing tumors and body regions, such as the prostate, where there could be dramatic changes in organ position during each treatment.

Imaging Prostate Cancer More Clearly

Prostate cancer is the most common type of cancer in men in the United States. In 2023, an estimated 288,300 new cases will be diagnosed and 34,700 men will die from the disease.

Prostate cancer that is confined to the prostate is usually treated with surgery or radiation therapy. Unfortunately, many patients with primary prostate cancer have detectable metastases in their pelvic lymph nodes, which are correlated with a risk for cancer recurrence. Surgical procedures known as pelvic lymph node dissection or pelvic lymphadenectomy are used to detect pelvic node lesions, but their use is imprecise and limited to a planned surgical area. An ideal detection method for metastatic prostate cancer would locate tumors in pelvic nodes as well as more distant sites. The more precise a patient’s diagnosis, the easier it is for a health care provider to tailor the treatment to ensure that it is as effective and safe as possible. Notably, despite surgery or radiotherapy many patients with prostate cancer have local or distal recurrences within 10 years.

Among the tools physicians use to make cancer diagnoses is positron emission tomography–computed tomography (PET–CT or PET), a form of imaging that can help physicians precisely locate the position of a patient’s cancer within the body and determine the extent to which the cancer may have spread. Before a PET scan, patients are injected with a radioactive imaging agent. The PET scan detects cancer by identifying where in the body the radioactive agent accumulates.

In May 2023, FDA approved flotufolastat fluorine-18 (Posluma) for PET imaging of PSMA-positive lesions in patients with prostate cancer with suspected metastasis or with suspected recurrence based on elevated serum PSA level. PSA is a secreted biochemical marker that is used to screen individuals for prostate cancer and for predicted recurrence of the disease among patients who have received treatment. PSMA is a protein that is present in abundance on the surface of more than 90 percent of primary and metastatic prostate cancer cells. Flotufolastat F-18 contains a short peptide sequence that binds to PSMA and is internalized by cells that express PSMA. Flotufolastat F-18 also contains the radioisotope fluorine-18 which enables PET imaging of the prostate and other areas of the body where prostate cancer may have spread. Clinicians can use this information to decide which patient should receive treatment and spare others from unnecessary procedures.

Findings from two clinical trials that FDA used to approve flotufolastat F-18 indicate that detection of prostate cancers using this approach may help physicians make the best treatment decisions for patients ( 380 ) The ASCO Post Staff. FDA Approves Flotufolastat Fluorine-18 Injection, First Radiohybrid PSMA-Targeted PET Imaging Agent for Prostate Cancer. Accessed: July 5, 2023. . One study demonstrated a higher specificity of flotufolastat F-18 for the detection of pelvic lymph node metastasis, compared to standard histopathology, in patients with PSMA-positive lesions. Flotufolastat F-18 provided valuable information that would likely result in changes in clinical management for these patients. In the second study, flotufolastat F-18 demonstrated high prostate cancer recurrence detection rates in patients who had suspected disease recurrence based on elevated PSA levels.

Cytotoxic chemotherapy—use of chemicals to kill cancer cells—was first introduced as a pillar of cancer treatment in the early to mid-20th century ( 349 ) DeVita VT, Jr., et al. (2008) Cancer Res, 68: 8643. [LINK NOT AVAILABLE] . Chemotherapy remains a backbone of cancer treatment and its use is continually evolving to minimize potential harms to patients with cancer, while maximizing its benefits.

As with surgery, chemotherapy is more commonly used to treat cancer in combination with one or more additional types of treatments. Furthermore, FDA continues to grant approvals to newer and more effective chemotherapeutics. FDA also routinely expands the use of previously approved chemotherapeutics for additional cancer types through review of new clinical trials as well as by monitoring of current real-world use of such agents. The FDA Project Renewal leverages expertise of clinical researchers to review existing published literature on drug utilization and maintain updated labeling of older, commonly prescribed anticancer therapeutics. As one example of this approach, in December 2022, FDA approved updated labeling for the chemotherapeutic capecitabine (Xeloda) which included new indications and dosing regimens for capecitabine tablets.

Treatment with cytotoxic chemotherapeutics can have adverse effects on patients. These effects can occur during treatment and continue in the long term, or they can appear months or even years later. Health care providers and researchers are investigating different approaches to make chemotherapeutics safer for patients. Areas of ongoing investigation include designing modifiable chemotherapeutics, e.g., with “on” and “off ” switches, that are selectively delivered to tumors while sparing healthy tissue; evaluating less aggressive chemotherapy regimens which can allow patients the chance of an improved quality of life without compromising survival; and identifying biomarkers such as circulating tumor DNA to correctly predict which patients will or will not benefit from chemotherapy, among other approaches ( 381 ) East P, et al. (2022) Nat Commun, 13: 5632. [LINK NOT AVAILABLE] ( 382 ) Rais R, et al. (2022) Sci Adv, 8: eabq5925. [LINK NOT AVAILABLE] ( 383 ) Kotani D, et al. (2023) Nat Med, 29: 127. [LINK NOT AVAILABLE] .

Notably, due to complex reasons, the United States is amid a significant chemotherapeutic shortage. The situation is affecting many patients and disrupting clinical research nationwide. It is imperative that all stakeholders in health care come together and identify ways to address these shortages at the earliest possible time (see Addressing Cancer Drug Shortages ).

Remarkable advances in our understanding of the biology of cancer, including the identification of numerous genetic mutations that fuel tumor growth, set the stage for a new era of precision medicine, an era in which the standard of care for many patients is changing from a one-size-fits-all approach to one in which greater understanding of the individual patient and the characteristics of his or her cancer dictates the best treatment option for the patient (see Understanding the Path to Cancer Development ).

Therapeutics directed to molecules influencing cancer cell multiplication and survival target tumor cells more precisely than cytotoxic chemotherapeutics, which generally target all rapidly dividing cells, and thereby limit damage to healthy tissues. The greater precision of these molecularly targeted therapeutics tends to make them more effective and less toxic than cytotoxic chemotherapeutics. As a result, they are not only saving the lives of patients with cancer, but also allowing these individuals to have a higher quality of life. Unfortunately, because of multilevel barriers to health care, there are disparities in the utilization of molecularly targeted treatments among patients from racial and ethnic minorities and other medically underserved populations ( 13 ) American Association for Cancer Research. AACR Cancer Disparities Progress Report 2022. Accessed: June 30, 2023. . It is vital that ongoing research and future public health policies are aimed to ensure equitable access to precision cancer medicine including tumor genetic testing and the receipt of molecularly targeted therapeutics for all patients.

In the 12 months spanning August 1, 2022, to July 31, 2023, FDA approved seven new molecularly targeted anticancer therapeutics (see Table 3 ). During this period, FDA also approved nine previously approved molecularly targeted anticancer therapeutics for treating additional types of cancer.

Expanding Treatment Options for Patients with Lung Cancer

Lung cancer is the second most diagnosed cancer in both men and women and the most common cause of cancer death. More than 127,000 deaths are estimated to occur from the disease in 2023 in the United States ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Decades of basic and translational research have significantly increased our understanding of the genetic changes that drive lung cancer growth and have fueled the development of therapeutics that target these changes (see Figure 1 ) ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Two recent FDA decisions have the potential to drive more progress against lung cancer because they have provided new molecularly targeted therapeutic options for certain patients with the disease.

About 81 percent of lung cancers diagnosed in the United States are classified as non–small cell lung cancers (NSCLC) and approximately 25 percent of patients with NSCLC carry mutations in the gene that is responsible for producing KRAS, an essential protein needed for growth and survival of normal lung cells, but which can contribute to cancer if mutated ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. ( 384 ) Janne PA, et al. (2022) N Engl J Med, 387: 120. [LINK NOT AVAILABLE] . Mutated KRAS represents one of the most common genetic alterations responsible for the development and progression of human cancers. Patients with NSCLC harboring KRAS mutations often develop resistance to standard treatments such as chemotherapy, radiation therapy, and immunotherapy, and only 25 percent of these patients live five years or more after diagnosis ( 438 ) Voruganti T, et al. (2023) JAMA Oncol, 9: 334. [LINK NOT AVAILABLE] . The most common KRAS mutation in patients with NSCLC is known as KRAS G12C, an alteration that is more frequently found in individuals who smoke currently or have smoked previously. The G12C mutation causes KRAS protein to prefer an “on” or “active” state, leading to uncontrollable cell growth that can form tumors.

Historically, KRAS has been considered an undruggable target because of the difficulties in designing a therapeutic that could selectively bind and inhibit KRAS in cancers. Despite major breakthroughs in selective targeting of a range of other genetic drivers of NSCLC, no effective treatment options were available for patients with KRAS G12C until two years ago. Thanks to enhanced understanding of KRAS biology and unprecedented progress in structural biology and drug development, in May 2021, sotorasib (Lumakras) became the first ever molecularly targeted therapeutic approved by the FDA for the treatment of patients with NSCLC with the KRAS G12C mutation (see Figure 16 ) ( 4 ) American Association for Cancer Research. AACR Cancer Progress Report 2021. Accessed: June 30, 2023. .

In December 2022, FDA approved a new molecularly targeted therapeutic, adagrasib (Krazati), for adult patients with locally advanced or metastatic NSCLC that has the KRAS G12C mutation, as determined by an FDA-approved test, and who have received at least one prior systemic treatment such as chemotherapy or immunotherapy. The FDA also approved companion diagnostics (see Sidebar 34 ), QIAGEN therascreen KRAS RGQ PCR kit (tumor tissue-based) and Agilent Resolution ctDx FIRST Assay (blood-based) to help identify patients with NSCLC carrying the KRAS G12C mutation. Both sotorasib and adagrasib bind to KRAS G12C protein and lock it in an inactive state thus blocking tumor growth.

The FDA approval of adagrasib was granted after it was shown in a phase II clinical trial that 43 percent of the patients who received the targeted therapeutic had complete or partial tumor shrinkage and continued to respond for a median of 8.5 months without their cancer progressing ( 384 ) Janne PA, et al. (2022) N Engl J Med, 387: 120. [LINK NOT AVAILABLE] . A critical finding from the clinical trial was that adagrasib was able to reach the brains of patients with NSCLC and shrink tumors that had metastasized to the brain ( 385 ) Kotecha R, et al. (2022) N Engl J Med, 387: 1238. [LINK NOT AVAILABLE] . While additional research is needed to confirm therapeutic activity in the brain, these data are extremely encouraging considering recent findings that 27 to 42 percent of patients with NSCLC whose tumors harbor the KRAS G12C mutation may have central nervous system (CNS) metastases at diagnosis, and such metastases are associated with a poor prognosis ( 384 ) Janne PA, et al. (2022) N Engl J Med, 387: 120. [LINK NOT AVAILABLE] .

Another major advance against lung cancer during the 12 months covered in this report is the FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) for adult patients with surgically unremovable or metastatic NSCLC whose tumors have a type of mutation in the human epidermal growth factor receptor 2 (HER2) gene, called an activating mutation, as detected by an FDA-approved test, and who have received a prior systemic therapy. The FDA also approved Oncomine Dx Target Test (tissue-based) and Guardant360 CDx (blood-based) as companion diagnostics to test patients for activating HER2 mutations.

HER2-mutated NSCLC, which accounts for three percent of all NSCLC cases, is associated with female sex, never-smoking history, and a poor prognosis. Furthermore, this type of NSCLC has a higher incidence of brain metastases than NSCLC without HER2 mutations or with other mutations ( 386 ) Li BT, et al. (2022) N Engl J Med, 386: 241. [LINK NOT AVAILABLE] ( 387 ) Riudavets M, et al. (2021) ESMO Open, 6: 100260. [LINK NOT AVAILABLE] .

Fam-trastuzumab deruxtecan-nxki is a type of molecularly targeted therapeutic called an antibody–drug conjugate. It comprises a cytotoxic agent, deruxtecan, attached to the HER2-targeted antibody, trastuzumab (Herceptin), by a linker. When the antibody attaches to HER2 protein on the surface of lung cancer cells, the antibody–drug conjugate is internalized by the cells. This leads to deruxtecan being released from the linker and the antibody. Once free, the deruxtecan is toxic to the cancer cells, which ultimately die.

The approval of fam-trastuzumab deruxtecan-nxki was primarily based on the results of a phase II clinical trial in which treatment with the HER2-targeted therapeutic shrank tumors in nearly 60 percent of the study participants ( 388 ) National Cancer Institute. Enhertu Approved for Lung Cancer. Accessed: July 5, 2023. . Among patients whose tumors shrank, the treatment kept their lung cancer at bay for nearly 9 months. While fam-trastuzumab deruxtecan-nxki has previously been approved for the treatment of patients with HER2-driven breast and gastric cancers (4,389), this was the first approval of a HER2-targeted therapeutic for NSCLC and provides new hope for patients with NSCLC who carry an activating HER2 mutation.

Like most cancer treatments, fam-trastuzumab deruxtecan-nxki can have adverse effects, some of which can be severe. One of the most concerning and, in the case of NSCLC, life threatening, is interstitial lung disease which causes stiffness in the lungs, making it difficult to breathe and get oxygen to the bloodstream. Therefore, FDA approved fam-trastuzumab deruxtecan-nxki with a warning for interstitial lung disease and recommends that patients being treated with the molecularly targeted therapeutic be monitored for signs and symptoms of interstitial lung disease, including cough, dyspnea (difficult or labored breathing), fever and other new or worsening respiratory symptoms. If interstitial lung disease is suspected, further testing and intervention must be considered.

While FDA approvals of sotorasib, adagrasib and fam-trastuzumab deruxtecan-nxki are significant advances for patients with NSCLC, all stakeholders in public health need to work together to ensure that every patient has access to and benefits from the latest developments in precision cancer medicine. Patients with lung cancer who receive molecularly targeted therapies have better survival compared to those who do not receive targeted therapies ( 390 ) Goulart BHL, et al. (2021) Clin Lung Cancer, 22: e723. [LINK NOT AVAILABLE] ( 391 ) Lemmon CA, et al. (2023) JCO Precis Oncol, 7: e2200294. [LINK NOT AVAILABLE] . Unfortunately, according to recent data, many patients with advanced NSCLC do not receive appropriate molecular tests or the appropriate molecularly targeted treatments due to gaps in the delivery of clinical care ( 392 ) Osazuwa-Peters OL, et al. (2023) Clin Lung Cancer, 24: 305. [LINK NOT AVAILABLE] ( 393 ) Sadik H, et al. (2022) JCO Precis Oncol, 6: e2200246. [LINK NOT AVAILABLE] .

Targeting Cancers Based on a Common Genetic Feature, Not Tissue of Origin

Chromosomal translocations that involve the RET gene and lead to the production of activating RET fusion proteins (see Sidebar 7 ) are rare alterations observed mostly in patients with certain types of thyroid cancer and lung cancer ( 394 ) Duke ES, et al. (2023) Clin Cancer Res: OF1. [LINK NOT AVAILABLE] . In 2020, FDA approved the RET-targeted therapeutic, selpercatinib (Retevmo), for treating patients with metastatic NSCLC and certain thyroid cancers that test positive for chromosomal translocations involving the RET gene ( 389 ) Sengupta R, et al. (2020) Clin Cancer Res, 26: 5055. [LINK NOT AVAILABLE] .

In solid tumors other than lung cancer and thyroid cancer, RET gene fusions are rarer, observed in less than one percent of patients ( 394 ) Duke ES, et al. (2023) Clin Cancer Res: OF1. [LINK NOT AVAILABLE] . However, this is a distinct patient population since RET gene fusions are mutually exclusive of other genetic alterations and provide a unique opportunity for therapeutic intervention ( 394 ) Duke ES, et al. (2023) Clin Cancer Res: OF1. [LINK NOT AVAILABLE] . A recent decision from FDA offers a new treatment option for these patients who until this approval had no molecularly targeted therapeutics available for their cancer.

In September 2022, FDA expanded the approval of selpercatinib for the treatment of adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. The approval of selpercatinib was based on the results of a phase I/II basket clinical trial (see Figure 14 ) in which treatment with the RET-targeted therapeutic shrank tumors in nearly 44 percent of the study participants ( 395 ) Subbiah V, et al. (2022) Lancet Oncol, 23: 1261. [LINK NOT AVAILABLE] . Patients with a range of cancer types including pancreatic adenocarcinoma, colorectal, salivary gland, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma responded to selpercatinib, emphasizing the importance of basket clinical trial designs in driving progress in precision medicine.

Delivering a Cytotoxic Drug Precisely to Ovarian Cancer Cells

In 2023, an estimated 19,710 new cases of ovarian cancer will be diagnosed in the United States, and 13,270 women will die from the disease ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Many patients with ovarian cancer are diagnosed at an advanced stage. Patients with advanced disease are usually treated with platinum-based chemotherapeutics. Although most patients respond initially to platinum-based treatment, nearly 80 percent will experience relapse. Unfortunately, patients with recurrent ovarian cancer are resistant to platinum-based treatments and have a poor prognosis.

Folate receptor alpha (FRα) is a cell surface protein that binds to and transports folate (also known as vitamin B9) into cells. Research has shown that FRα is expressed at much higher levels in advanced ovarian cancer cells, compared to healthy adult tissues ( 396 ) Dilawari A, et al. (2023) Clin Cancer Res, OF1. [LINK NOT AVAILABLE] . There is also emerging evidence, including clinical data, that elevated FRα expression may be associated with lack of response to standard chemotherapy in ovarian cancer ( 397 ) Matulonis UA, et al. (2023) J Clin Oncol, 41: 2436. [LINK NOT AVAILABLE] . These attributes make FRα a promising target for therapeutic intervention in ovarian cancer.

The molecularly targeted therapeutic mirvetuximab soravtansine-gynx (Elahere) targets FRα and, in November 2022, received FDA approval for adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. FDA also approved the companion diagnostic VENTANA FOLR1 RxDx Assay to identify patients eligible for the therapy.

Mirvetuximab soravtansine-gynx is an antibody–drug conjugate designed to deliver a cytotoxic drug to cells that express FRα. It is the first antibody–drug conjugate to be approved by FDA to treat platinum-resistant ovarian cancer and marks the first FDA approval since 2014 for platinum chemotherapy-resistant ovarian cancer, which is associated with a poor prognosis. The approval was based on results from a phase III clinical trial that enrolled 106 patients. Nearly 32 percent of patients responded to mirvetuximab soravtansine-gynx, with a median duration of response of 6.9 months ( 396 ) Dilawari A, et al. (2023) Clin Cancer Res, OF1. [LINK NOT AVAILABLE] ( 397 ) Matulonis UA, et al. (2023) J Clin Oncol, 41: 2436. [LINK NOT AVAILABLE] . The approval of mirvetuximab soravtansine-gynx is great news for patients, such as Jacly n (Jackie) VanRaaphorst . There is preliminary evidence that mirvetuximab soravtansine-gynx also improves overall survival for this FRα-positive ovarian cancer patient population ( 398 ) Angelergues A, et al. (2023) Journal of Clinical Oncology, 41: LBA5507. [LINK NOT AVAILABLE] .

A common adverse effect of mirvetuximab soravtansine-gynx is ocular toxicity—changes that affect the structure or function of the eye. Therefore, FDA approved mirvetuximab soravtansine-gynx with a warning that patients being treated with the molecularly targeted therapeutic be monitored and treated for signs and symptoms of vision impairment and corneal disorders.

Improving Outcomes for Patients with Metastatic Breast Cancer

Despite major advances in the treatment of breast cancer, it remains the second leading cause of cancer-related death for women in the United States ( ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Recent FDA decisions have the potential to power more progress against breast cancer because they have provided new therapeutic options for certain patients with the disease.

For patients with breast cancer, one factor determining what treatment options should be considered is the presence or absence of three tumor biomarkers, estrogen and progesterone hormone receptors, which drive tumor growth upon engagement with their respective hormones, and the protein HER2. About 70 percent of breast cancers diagnosed in the United States are characterized as hormone receptor–positive and HER2-negative ( 3 ) Giaquinto AN, et al. (2022) CA Cancer J Clin, 72: 524. [LINK NOT AVAILABLE] . Potential treatment options for these patients include the combination of an antihormone therapeutic such as tamoxifen, which works by preventing the hormone estrogen from attaching to its receptor; or letrozole, which works by lowering the level of estrogen in the body; or fulvestrant, which works by destroying estrogen receptors (ER) with a cyclin-dependent kinase 4/6 inhibitor. Treatment with antihormone therapeutics is also called endocrine therapy.

Unfortunately, most advanced, hormone receptor-positive breast cancers that initially respond to endocrine therapy eventually become treatment resistant (see Sidebar 35 ). Resistance to fulvestrant commonly develops due to mutations in ESR1, the gene that encodes the ER protein. Until recently, fulvestrant was the only available FDA-approved treatment that worked by destroying ER. Therefore, patients whose tumors become resistant to it were left with limited treatment options.

The FDA approval of elacestrant (Orserdu) in January 2023 brings new hope to these patients. Elacestrant, which also works by destroying the ER, was approved for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Unlike fulvestrant, which is delivered through intramuscular injections, elacestrant is administered orally, making it more convenient for patients to receive the treatment. The approval was based on results from a phase III, randomized clinical trial showing that among patients with ESR1 mutations, those treated with elacestrant had a 45 percent lower risk of death or disease progression than those treated with other endocrine therapies ( 399 ) Bidard FC, et al. (2022) J Clin Oncol, 40: 3246. [LINK NOT AVAILABLE] .

Personalizing Treatment for Patients with a Rare Solid Tumor

Rare cancer is defined by the National Cancer Institute as cancer that occurs in fewer than 15 out of 100,000 people each year. Rare cancers can be challenging for researchers to study and for physicians to treat (see Sidebar 36 ). During the 12 months covered by this report, August 1, 2022, to July 31, 2023, the FDA approved molecularly targeted therapeutics and immunotherapeutics for treating several rare cancers, bringing the promise of precision medicine to patients, such as Isabella (Bella) Snow Fraser, p. 110, and Alexis Browning, p. 112, who often have few treatment options.

Bile duct cancer, also known as cholangiocarcinoma, is a rare but aggressive disease in which cancer arises from cells in the bile ducts. Cholangiocarcinoma is often diagnosed at an advanced stage. There are two types of bile duct cancer: intrahepatic, where cancer forms in the bile ducts inside the liver; and extrahepatic, where cancer forms in the bile ducts outside the liver. Less than 8,000 new cases of bile duct cancer are estimated to be diagnosed in the United States in 2023 and only a small number of bile duct cancers are intrahepatic ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . While rare, the incidence of intrahepatic cholangiocarcinoma is increasing worldwide ( 400 ) Goyal L, et al. (2023) N Engl J Med, 388: 228. [LINK NOT AVAILABLE] . Surgery is the main curative treatment option for patients with intrahepatic cholangiocarcinoma. However, up to two thirds of patients have disease recurrence and patients with intrahepatic cholangiocarcinoma have a 5-year overall survival rate of less than eight percent ( 400 ) Goyal L, et al. (2023) N Engl J Med, 388: 228. [LINK NOT AVAILABLE] .

Alterations in fibroblast growth factor receptor 2 (FGFR2), a protein involved in many cellular processes including multiplication, migration, and survival, are associated with several cancers including bile duct cancers. Nearly 14 percent of patients with intrahepatic cholangiocarcinoma have fusions or rearrangements in the FGFR2 gene (see Sidebar 7 ) ( 400 ) Goyal L, et al. (2023) N Engl J Med, 388: 228. [LINK NOT AVAILABLE] . FDA had previously approved two molecularly targeted therapeutics, pemigatinib (Pemazyre) and infigratinib (Truseltiq), which block the function of FGFR2 proteins, for the treatment of patients with cholangiocarcinoma with confirmed FGFR2 fusions or rearrangements ( 389 ) Sengupta R, et al. (2020) Clin Cancer Res, 26: 5055. [LINK NOT AVAILABLE] ( 401 ) Sengupta R, et al. (2021) Clin Cancer Res, 27: 5757. [LINK NOT AVAILABLE] . While these agents are benefiting many patients with bile duct cancer, their efficacy has been somewhat limited due to the development of treatment resistance ( 400 ) Goyal L, et al. (2023) N Engl J Med, 388: 228. [LINK NOT AVAILABLE] .

In September 2022, the FDA granted approval to a third FGFR2-targeted therapeutic, futibatinib (Lytgobi) for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma that tests positive for FGFR2 fusions or other rearrangements. The approval was based on the results of a phase I/II clinical trial that showed that futibatinib shrank tumors in 42 percent of patients ( 400 ) Goyal L, et al. (2023) N Engl J Med, 388: 228. [LINK NOT AVAILABLE] . The median duration of response was 9.7 months. Futibatinib works differently than pemigatinib and infigratinib and preliminary data indicate that it may mitigate the challenge of treatment resistance since patients who had disease progression after prior FGFR-targeted therapy with other inhibitors maintained sustained clinical benefit with futibatinib ( 400 ) Goyal L, et al. (2023) N Engl J Med, 388: 228. [LINK NOT AVAILABLE] .

Combining Molecularly Targeted Therapeutics to Block Tumor Growth

The BRAF enzyme has a critical role in controlling cell growth. The BRAF gene is altered in approximately six percent of all human cancers, including melanoma and colorectal cancer ( 402 ) Dankner M, et al. (2018) Oncogene, 37: 3183. [LINK NOT AVAILABLE] . Most cancer-related changes in the BRAF gene cause the protein to continuously stay active, thus helping cancer cells grow faster than normal cells. One of the most common cancer-related changes is the BRAF gene is called the BRAF V600E mutation. Presence of the BRAF V600E mutation is associated with poor outcomes for patients with certain types of cancer.

The first time FDA approved the use of two molecularly targeted therapeutics as a combination treatment for cancer was in January 2014 ( 67 ) Arteaga CL, et al. (2014) Clin Cancer Res, 20: S1. [LINK NOT AVAILABLE] . The approval was for the use of dabrafenib (Tafinlar) and trametinib (Mekinist) for treating patients with metastatic melanoma that tests positive for activating BRAF V600E and BRAF V600K mutations. The two therapeutics target different components of the BRAF signaling pathway. Dabrafenib targets altered BRAF proteins containing V600 mutations, while trametinib targets MEK1 and MEK2, which are two proteins that mediate the function of BRAF. By blocking both BRAF and MEK, the combination therapy can more completely and effectively shut down the signaling pathway. The combination was approved after it was shown to almost double the length of time before disease progression compared with dabrafenib alone ( 403 ) Flaherty KT, et al. (2012) N Engl J Med, 367: 1694. [LINK NOT AVAILABLE] .

In March 2023, the same combination of molecularly targeted therapeutics was approved for pediatric patients one year of age and older with low-grade glioma with a BRAF V600E mutation who require systemic therapy. The FDA also approved new oral formulations of dabrafenib and trametinib for pediatric patients who are unable to swallow pills.

Brain and other nervous system tumors are the second most diagnosed cancers in children. Low-grade glioma is the most common type of pediatric brain cancer. Research has demonstrated that BRAF signaling pathway activation is common in pediatric low-grade gliomas. Therefore, the March approval of dabrafenib and trametinib combination therapy brings hope to many parents and families whose children are diagnosed with the disease. FDA approved the combination therapy based on data from a clinical trial showing that a significantly higher percentage of patients who received dabrafenib and trametinib had their tumors shrink compared to those who received the standard of care chemotherapy (47 percent vs. 11 percent, respectively) ( 404 ) Hargrave DR, et al. (2022) J Clin Oncol, 40: 2009. [LINK NOT AVAILABLE] . Patients treated with dabrafenib and trametinib also had a 69 percent lower risk of disease progression, with a progression-free survival of 20 months, compared to seven months among patients receiving chemotherapy ( 404 ) Hargrave DR, et al. (2022) J Clin Oncol, 40: 2009. [LINK NOT AVAILABLE] .

The FDA approval of a second combination therapy during the 12 months covered in the report provides a new and first of a kind treatment option for certain patients with colorectal cancer. The combination of tucatinib (Tukysa) and trastuzumab (Herceptin), both HER2-targeted therapeutics, was approved by FDA in January 2023 for patients with HER2-positive unresectable or metastatic colorectal cancer that has progressed following at least two standard treatments, including chemotherapy. To be eligible to receive the new combination, patients’ tumors must also not have driver mutations in the RAS group of genes.

Colorectal cancer is the second most common cause of cancer death in the United States. An estimated 153,020 people are expected to be diagnosed with colorectal cancer in the United States in 2023 ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Excessive production of the HER2 protein which leads to tumor cell multiplication, invasion, and metastasis is found in approximately three to five percent of patients with metastatic colorectal cancers ( 405 ) Ahcene Djaballah S, et al. (2022) Am Soc Clin Oncol Educ Book, 42: 1. [LINK NOT AVAILABLE] such as that of B rian Beck . The approval of the tucatinib and trastuzumab combination for this patient population was based on a phase II clinical trial which showed that 38 percent of patients who received the drug combination had their tumors shrink or disappear ( 406 ) Strickler JH, et al. (2023) Lancet Oncol, 24: 496. [LINK NOT AVAILABLE] .

Considering that prior treatment options for patients with HER2-positive colorectal cancer that has returned or started growing again after receiving standard treatments were not very effective, the approval of tucatinib and trastuzumab represents a significant breakthrough for this subset of patients with metastatic colorectal cancer. Ongoing studies are evaluating whether addition of tucatinib and trastuzumab to standard treatment regimens could be used earlier on as the initial treatment for metastatic HER2-positive colorectal cancer.

Adding Precision to the Treatment of Blood Cancers

Cancers that arise in blood-forming tissues, such as the bone marrow, or in cells of the immune system, are called blood cancers, or hematologic cancers. In the 12 months covered by this report, FDA has made numerous decisions that are transforming the lives of patients with a wide array of hematologic cancers (see Sidebar 37 ).

Acute myeloid leukemia (AML) is the most commonly diagnosed leukemia in the United States, with 20,380 new cases anticipated in 2023 ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . AML has only 32 percent overall 5-year relative survival rate, the lowest among leukemias ( 5 ) Surveillance, Epidemiology, and End Results (SEER) Program. Accessed: July 5, 2023. . Research has substantially increased our understanding of the biology of AML, in particular the different types of genetic mutations that promote AML development. This knowledge is fueling the emergence of molecularly targeted therapeutics for defined groups of patients with the disease.

One of the genes known to be mutated in about seven to 14 percent of AML cases is IDH1 ( 407 ) de Botton S, et al. (2023) Blood Adv, 7: 3117. [LINK NOT AVAILABLE] . Mutation in IDHI gene results in an altered IDH1 protein, which can drive cancer formation by interfering with normal cellular maturation and promote uncontrolled cell multiplication. This knowledge led to the development of ivosidenib (Tibsovo), the first therapeutic to target IDH1, which was approved by FDA in 2018.

In December 2022, FDA approved a second IDH1-targeted agent, olutasidenib (Rezlidhia), for adult patients with AML that has not responded to or has relapsed after other treatments, and that harbors an IDH1 mutation as detected by an FDA-approved test. At the same time that the molecularly targeted therapeutic was approved, FDA also approved the companion diagnostic, Abbott RealTime IDH1 Assay, to identify patients with AML with an IDH1 mutation.

Olutasidenib was approved for the treatment of AML after it was shown in a phase I/II clinical trial that 32 percent of patients treated with the molecularly targeted therapeutic had complete remission, meaning that there was no evidence of disease and full recovery of blood counts ( 407 ) de Botton S, et al. (2023) Blood Adv, 7: 3117. [LINK NOT AVAILABLE] . Not only does the approval of olutasidenib increase treatment options for patients with IDH1-mutated AML, but there is also preliminary evidence that patients may respond longer to olutasidenib compared to the other IDHI-targeted therapy ( 407 ) de Botton S, et al. (2023) Blood Adv, 7: 3117. [LINK NOT AVAILABLE] . A potential side effect observed among patients treated with olutasidenib is differentiation syndrome. The condition is caused by a large, rapid release of immune molecules called cytokines from leukemia cells and can lead to fever, cough, troubled breathing, build-up of excess fluid around the heart and lungs, low blood pressure, and kidney failure, but is generally readily treated with full resolution. The FDA approval is accompanied by a warning highlighting the risk of this potentially fatal adverse effect.

In July 2023, the FDA approved a second new molecularly targeted therapeutic, quizartinib (Vanflyta), for the treatment of AML. Quizartinib was approved for treating adults who have newly diagnosed AML that tests positive for a mutated FLT3 gene known as FLT3 internal tandem duplication (ITD). Mutations in the FLT3 gene promote the multiplication and survival of AML cells in 25 to 30 percent of cases, and patients with this type of AML have particularly poor outcomes ( 408 ) Yanada M, et al. (2005) Leukemia, 19: 1345. [LINK NOT AVAILABLE] . The approval was based on results from a phase III clinical trial showing that patients who received quizartinib had a 22 percent reduced risk of death compared to those who received standard chemotherapy during the course of the clinical study ( 409 ) Erba HP, et al. (2023) Lancet, 401: 1571. [LINK NOT AVAILABLE] . Quizartinib can cause several cardiac adverse effects and is therefore available only through a restricted program.

At the same time that the FDA made the decision about quizartinib, it expanded the use of the LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic to identify patients with FLT3 ITD mutation–positive AML who are eligible for treatment with the new molecularly targeted therapeutic.

Myeloid/lymphoid neoplasm (MLN) with fibroblast growth factor receptor 1 (FGFR1) rearrangement is a rare, aggressive disease characterized by higher-than-normal levels of certain white blood cells. MLNs do not respond well to standard chemotherapy and can rapidly progress to AML ( 410 ) Verstovsek S, et al. (2018) Ann Oncol, 29: 1880. [LINK NOT AVAILABLE] . FGFR1 is a cell surface protein that stimulates cellular proliferation upon binding with specific extracellular molecules. In rare instances, the FGFR1 gene fuses with another gene (an alteration known as a genetic rearrangement) resulting in a fusion protein that drives the development of MLNs.

Pemigatinib (Pemazyre) inhibits the function of FGFR1 to suppress the growth of FGFR1-driven cancers ( 410 ) Verstovsek S, et al. (2018) Ann Oncol, 29: 1880. [LINK NOT AVAILABLE] and in August 2022, it was approved by FDA for adults with MLNs with FGFR1 rearrangement who have not responded to or have relapsed after other treatments. The approval was based on results from a phase II clinical trial that showed that 79 percent of patients had a complete response to pemigatinib. Therefore, the FDA approval of pemigatinib for adult patients with relapsed or refractory MLNs with FGFR1 alteration is a major milestone for the treatment of patients who are diagnosed with the disease.

Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed blood cancer in the United States. In 2023, 77,240 people in the United States are expected to be newly diagnosed with the disease ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Notably, NHL encompasses many different types of cancer, most of which arise in immune cells called B cells. Two molecularly targeted therapeutics, recently approved by FDA for treating different subtypes of NHL arising in B cells— pirtobrutinib (Jaypirca) and zanubrutinib (Brukinsa)—target a protein called Bruton tyrosine kinase (BTK). BTK was first identified in 1993. Since its discovery, the role of BTK has been studied extensively in blood cancers and inflammatory diseases. Researchers have found that BTK is a key component of a signaling pathway that promotes the survival and expansion of NHL B cells. Consequently, BTK inhibitors have revolutionized the treatment of NHL arising in B-cells, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) as well as certain inflammatory diseases ( 411 ) Alu A, et al. (2022) J Hematol Oncol, 15: 138. [LINK NOT AVAILABLE] .

Ibrutinib was the first BTK inhibitor approved by FDA. The approval, in 2013, was for the treatment of patients with relapsed and refractory mantle cell lymphoma (MCL). While the approval of ibrutinib was a major milestone in personalized treatment for B-cell cancers, researchers soon discovered that in patients on continuous treatment with BTK-targeted therapy, cancer cells can acquire mutations in the BTK gene that render the therapeutic ineffective. Since then, newer and more sophisticated BTK inhibitors with improved specificities and thus reduced toxicities have been developed to mitigate the challenge of acquired resistance (see Sidebar 35 ).

Pirtobrutinib (Jaypirca) is a new BTK targeted therapeutic that FDA approved in January 2023 for treating MCL. The agent was approved for patients with relapsed or refractory MCL that has not responded to or has relapsed after another treatment, including a BTK inhibitor. Pirtobrutinib has a unique mechanism of action that makes it effective even against mutated forms of BTK that are resistant to other BTK-targeted therapeutics ( 412 ) Zhang J, et al. (2022) Biomark Res, 10: 17. [LINK NOT AVAILABLE] . The approval of pirtobrutinib was based on results from a phase I/II clinical trial, which showed that 50 percent of MCL patients treated with the molecularly targeted therapeutic had tumor shrinkage, with 13 percent having their tumors disappear.

Zanubrutinib, another BTK-targeted therapeutic, was approved for treating patients with MCL in November 2019 ( 413 ) Sengupta R, et al. (2020) Cancer Epidemiol Biomarkers Prev, 29: 1843. [LINK NOT AVAILABLE] . In January 2023, FDA approved zanubrutinib for treating adults who have CLL or SLL, which are slow-growing types of NHL. CLL and SLL are essentially the same disease but have different names depending on where in the body the NHL cells accumulate. CLL cells are found mostly in the blood and bone marrow, whereas SLL cells are found mostly in the lymph nodes.

The approval of zanubrutinib to treat CLL and SLL was based on results from two phase III clinical trials. The first trial which evaluated the efficacy of zanubrutinib in previously untreated patients with CLL/SLL showed that patients who received zanubrutinib lived a longer time without their cancer worsening compared with patients who received standard treatments. In the second trial, which compared zanubrutinib to ibrutinib in CLL/SLL patients whose disease did not respond to or came back after prior treatments, a greater percentage of patients receiving zanubrutinib were alive during the course of the study with no growth of their cancer, compared to patients taking ibrutinib ( 414 ) Brown JR, et al. (2023) N Engl J Med, 388: 319. [LINK NOT AVAILABLE] .

Blocking Progression of Metastatic Prostate Cancers

Prostate cancer is the most commonly diagnosed cancer among men living in the United States. In 2023 alone, more than 288,000 men are expected to be diagnosed with the disease ( 28 ) American Cancer Society. Cancer Facts and Figures. Accessed: July 5, 2023. . Research has shown that up to 30 percent of prostate cancers have mutations in genes that influence the homologous recombination repair (HRR) pathway (e.g., BRCA, ATM), a cellular process in which a group of proteins work together to repair DNA damage ( 415 ) de Bono J, et al. (2020) N Engl J Med, 382: 2091. [LINK NOT AVAILABLE] . Changes in the HRR pathway may result in the inability to repair DNA and lead to accumulation of mutations and cancer.

Poly-ADP ribose polymerase (PARP) proteins are central to a second type of DNA repair pathway called base excision repair. Researchers have found that breast, ovarian, pancreatic, and prostate cancers with genetic mutations that lead to HRR deficiency are responsive to PARP-targeted therapeutics because disruption of these two DNA repair pathways leads to pervasive DNA damage that kills cancer cells. In July 2023, FDA approved a PARP-targeted therapeutic, talazoparib (Talzenna) for treating certain groups of men with metastatic prostate cancer carrying mutations in genes that influence the homologous recombination DNA repair pathway.

Men, such as Colbert English, p. 96, who are diagnosed with metastatic prostate cancer are often treated initially with therapeutics that target androgens, the hormones that fuel prostate cancer growth. When the cancer stops responding to these treatments, it is referred to as castration-resistant prostate cancer. Talazoparib was approved in combination with the androgen-targeted therapeutic enzalutamide (Xtandi) for patients with HRR gene-mutated metastatic castration-resistant prostate cancer. Mutations in HRR genes such as BRCA1, BRCA2, and ATM were assessed prospectively using tumor tissue and/or blood-based DNA sequencing assays. The approval was based on results from a phase III clinical trial that showed that treatment with talazoparib significantly improved progression-free survival compared with treatment with enzalutamide alone ( 416 ) Agarwal N, et al. (2023) Lancet, 402: 291. [LINK NOT AVAILABLE] .

• A Message from AACR
• Executive Summary
• A Snapshot of a Year in Progress
• Cancer in 2023
• Understanding the Path to Cancer Development
• Reducing the Risk of Cancer Development
• Screening for Early Detection
• Spotlight on Immunotherapy: Pushing the Frontier of Cancer Medicine
• Perspective: Looking to the Future of Immunology
• Supporting Cancer Patients and Survivors
• Envisioning the Future of Cancer Science and Medicine
• Advancing the Future of Cancer Research and Care Through Evidence-based Policies
• AACR Call to Action
• AACR President’s Vision: Future of Cancer Research and Care
• AACR Cancer Progress Report 2023: Steering Committee

Your donation to the American Association for Cancer Research helps our more than 58,000 members worldwide drive progress against cancer.

Featured Topics

Featured series.

A series of random questions answered by Harvard experts.

Explore the Gazette

Read the latest.

Faster ‘in a dish’ model may speed up treatment for Parkinson’s

If it feels too hot to run, maybe it is

Does your brain reflect your sex?

Taha Rakhshandehroo (left) and Mohammad Rashidian in their lab.

Niles Singer/Harvard Staff Photographer

Fixing key flaw in revolutionary cancer treatment

Researchers devise way to boost CAR T-cell therapy to potentially ensure it doesn’t fade prematurely

Alvin Powell

Harvard Staff Writer

Researchers from Harvard Medical School and the Dana-Farber Cancer Institute have figured out how to give a timely boost to a revolutionary treatment that enlists immune cells in the anticancer fight, potentially bypassing a flaw that allows the therapy to fade before all diseased cells are gone.

The researchers, Mohammad Rashidian , assistant professor of cancer immunology at Dana-Farber and radiology at HMS, postdoctoral fellow Taha Rakhshandehroo, and their team created an enhancer protein that selectively energizes the anticancer cell therapy called CAR T-cells. This protein not only boosts the cells’ anticancer activity, it also promotes the development of memory CAR T-cells, which provide long-term immune protection against cancer, similar to the immune response after chicken pox infection or vaccination.

The cancer treatment, CAR-T cell therapy, was approved by federal regulators in 2017. It works by extracting immune T-cells from patients and reprograming them with a “chimeric antigen receptor” (CAR) on the cell surface. The receptor works like a lock and key for a protein marker on the surface of the cancer cells. That allows the CAR T-cells to recognize and attack cancer cells once they’re infused back into the body.

In recent years, CAR T-cell therapy has made headlines by working where conventional treatments failed, in some cases completely clearing cancer cells from the sickest patients.

But once the CAR T-cells have cleared most of the cancer, their numbers fade over time, allowing any remaining diseased cells to proliferate. For example, in multiple myeloma, a cancer of white blood cells, CAR T-cell therapy increases patients’ survival over the short term, but half of patients relapse within one to two years. Within three years, most patients see their cancers recur.

The advance, which has yet to be tested in humans, was developed using models of multiple myeloma in preclinical mice studies in work sponsored by Dana-Farber’s Innovation Research Fund Award, the Parker Institute for Cancer Immunotherapy, and a Blavatnik Therapeutics Challenge Award.

Results of the study were published recently in the journal Nature Biotechnology. The researchers said the procedure should be useful against other cancers, and have studies underway testing it against leukemia and lymphoma.

CAR T-cell therapy is one of a suite of relatively recent cancer treatments that have revolutionized care. Unlike traditional surgery, chemotherapy, and radiation therapy, the therapy turns the body’s own immune system into a powerful weapon to fight the disease.

The enhancer protein devised by Rashidian and Rakhshandehroo selectively targets CAR T-cells, enhancing their activity and persistence. The pair began the work two years ago with the goal of developing a procedure that could quickly translate to clinical care.

Other researchers have been addressing the CAR T-cell longevity problem for a decade by focusing on re-engineering them to extend their lifespan in the body, a strategy that largely fell short. Instead, Rashidian and Rahkshandehroo focused on stimulating the CAR-T cells post-infusion and at a desired time, rather than altering them.

To do so, they designed a protein that targets and stimulates CAR T-cells. The CAR receptor is the engineered part of the CAR T-cell that allows it to recognize cancer cells by detecting a specific marker on them.

The enhancer protein fuses the cancer marker to a molecule called IL-2, which enhances T-cell activity and persistence. The IL-2 is engineered to be weak so it does not affect normal T-cells, thus avoiding toxicities. However, because the enhancer protein targets CAR T-cells, the weak IL-2 enhances their activity through proximity.

“Sometimes in science, you see marginal differences here and there, and then you do the statistics, and you find out the significance,” Rakhshandehroo said. “For us, it was like night and day. Once we saw it, we knew there was something very robust happening here.”

Rakhshandehroo said subsequent experiments were aimed at illuminating specific questions about the process, but what impressed them was the persistence of the response despite shifting variables.

“We’ve tuned our experiments to be more specific, trying to answer specific questions, but what we’ve seen has always been very robust,” Rahkshandehroo said. “The door has been opened, and everyone can come and take advantage of the system and use it to understand the biology behind the enhancer’s impact on T-cells and their persistence as well as finding new therapies.”

To avoid overstimulating the CAR T-cells, Rashidian said they’ve tuned the enhancer protein to have a short circulatory half-life of just two hours before it clears from the body. That will give it time to stimulate the CAR T-cells without overstimulating them.

That also allows closer control of dosing once human trials begin — Rashidian has started the search for funding for a Phase 1 trial to gauge efficacy and safety. With such a short enhancer circulatory lifetime, Rashidian said, researchers can more easily adjust doses according to how patients respond in the trial.

“I’m very excited about it,” Rashidian said. “It works beyond what we have expected. It’s incredibly robust. I’m very hopeful that it will save patients’ lives.”

Share this article

You might like.

Could result in personalized models to test diagnostic and treatment strategies

Experts who have seen health consequences close-up offer guidelines for summer athletes 

Precision medicine is just one field where the answer matters

Garber to serve as president through 2026-27 academic year

Search for successor will launch in 2026

Finding right mix on campus speech policies

Legal, political scholars discuss balancing personal safety, constitutional rights, academic freedom amid roiling protests, cultural shifts

Good genes are nice, but joy is better

Harvard study, almost 80 years old, has proved that embracing community helps us live longer, and be happier

Explore  CRI’s 2023 Cancer Research Impact

Immunotherapy In-Depth

Gain in-depth knowledge about immunotherapy and the unique role your immune system plays in preventing, controlling, and eliminating a variety of cancers.

What is immunotherapy?

Cancer immunotherapy, also known as immuno-oncology, is a form of cancer treatment that uses the power of the body’s own immune system to prevent, control, and eliminate cancer.

Cancer immunotherapy comes in a variety of forms , including targeted antibodies, cancer vaccines, adoptive cell transfer, tumor-infecting viruses, checkpoint inhibitors, cytokines, and adjuvants. Immunotherapies are a form of biotherapy (also called biologic therapy or biological response modifier (BRM) therapy) because they use materials from living organisms to fight disease. Some immunotherapy treatments use genetic engineering to enhance immune cells’ cancer-fighting capabilities and may be referred to as gene therapies. Many immunotherapy treatments for preventing, managing, or treating different cancers can also be used in combination with surgery, chemotherapy, radiation, or targeted therapies to improve their effectiveness.

Immunotherapy can:

Educate the immune system to recognize and attack specific cancer cells, provide the body with additional components to enhance the immune response, boost immune cells to help them eliminate cancer, unleashing the power of the immune system is a smart way to fight cancer., it’s precise.

The immune system is precise, so it is possible for it to target cancer cells exclusively while sparing healthy cells.

It’s Dynamic

The immune system can adapt continuously and dynamically, just like cancer does, so if a tumor manages to escape detection, the immune system can re-evaluate and launch a new attack.

It Remembers

The immune system’s “memory” allows it to remember what cancer cells look like, so it can target and eliminate the cancer if it returns.

Why Immunotherapy

Immunotherapies have been approved in the United States and elsewhere to treat a variety of cancers and are prescribed to patients by oncologists. These approvals are the result of years of research and testing designed to demonstrate the effectiveness of these treatments. Immunotherapies are also available through clinical trials , which are carefully controlled and monitored studies involving patient volunteers.

Immunotherapy doesn’t always work for every patient, and certain types of immunotherapy are associated with potentially severe but manageable side effects. Scientists are developing ways to determine which patients are likely to respond to treatment and which aren’t. This research is leading to new strategies to expand the number of patients who may potentially benefit from treatment with immunotherapy.

Although scientists haven’t yet mastered all the immune system’s cancer-fighting capabilities, immunotherapy is already helping to extend and save the lives of many cancer patients. Immunotherapy holds the potential to become more precise, more personalized, and more effective than current cancer treatments—and potentially with fewer side effects. Learn more about how you can support new breakthroughs in cancer immunotherapy research .

Many cancer patients and caregivers may be familiar with traditional treatments, such as chemotherapy and radiation . Several important features of immunotherapy , a form of cancer treatment that uses the power of the body’s immune system to prevent, control and eliminate cancer, make for a more specific answer to cancer.

• Immunotherapy enables the  immune system  to recognize and target cancer cells, making it a universal answer to cancer.
• The list of cancers that are currently treated using immunotherapy is extensive.  See the full list of immunotherapies by cancer type .
• Immunotherapy has been an effective treatment for patients with certain types of cancer that have been resistant to chemotherapy and radiation treatment (e.g., melanoma).
• Immunotherapy can train the immune system to remember cancer cells. This “immunomemory” may result in longer-lasting remissions.
• Clinical studies on long-term  overall survival  have shown that the beneficial responses to cancer immunotherapy treatment are durable—that is, they may be maintained even after treatment is completed.
• Cancer immunotherapy is focused on the immune system and may be more targeted than conventional cancer treatments such as chemotherapy or radiation.
• Side effects vary according to each therapy and how it interacts with the body. Conventional cancer treatments have a direct effect of a chemical or radiological therapy on cancer and healthy tissues, which may result in common side effects such as hair loss and nausea.
• Side effects of cancer immunotherapy may vary depending on which type of immunotherapy is used. Potential side effects relate to overstimulation or misdirection of the immune system and may range from minor symptoms of inflammation (e.g., fever) to major conditions similar to autoimmune disorders.
• There are pros and cons to every cancer treatment. Speak with your oncology care team about immunotherapy and what is the best treatment plan for you.

Get more information

Resources, answers, and support.

Organizations that provide support and reliable answers for cancer patients and their loved ones

ImmunoGlossary

A comprehensive glossary that will help explain some of the terms you’ll come across on our website

Frequently Asked Immunotherapy Questions

What types of cancers can immunotherapy treat.

Immunotherapy has the potential to treat all cancers.

Immunotherapy enhances the immune system’s ability to recognize, target, and eliminate cancer cells, wherever they are in the body, making it a potential universal answer to cancer.

Immunotherapy has been approved in the U.S. and elsewhere as a first-line of treatment for several cancers, and may also be an effective treatment for patients with certain cancers that are resistant to prior treatment. Immunotherapy may be given alone or in combination with other cancer treatments. As of December 2019, the FDA has approved immunotherapies as treatments for nearly 20 cancers as well as cancers with a specific genetic mutation

Does immunotherapy have any side effects?

Immunotherapy may be accompanied by side effects that differ from those associated with conventional cancer treatments, and side effects may vary depending on the specific immunotherapy used. In most cases, potential immunotherapy-related side effects can be managed safely as long as the potential side effects are recognized and addressed early.

• Cancer immunotherapy treats the patient—by empowering their immune system—rather than the disease itself like chemotherapy and radiation. Patients may be tested for biomarkers that may indicate whether cancer immunotherapy would be an effective treatment.
• Side effects of immunotherapy may results from stimulation of the immune system and may range from minor inflammation and flu-like symptoms, to major, potentially life-threatening conditions similar to autoimmune disorders.
• Common side effects may include but are not limited to skin reactions, mouth sores, fatigue, nausea, body aches, headaches, and changes in blood pressure.

Conventional cancer treatments also have a range of side effects with a wide range of severity.

• Chemotherapy is intended to target fast-growing cancer cells, so it may damage other fast-growing normal cells in your body. Common side effects may include but are not limited to hair loss, nausea, diarrhea, skin rash, and fatigue.
• Radiation uses radioactive particles to destroy cancer cells in a localized area, so it may damage other healthy cells in that area. Side effects may be associated with the area of treatment, such as difficulty breathing when aimed at the chest, or nausea when aimed at the stomach. Skin problems and fatigue are common.
• The goal of surgery is to remove the cancerous tumor or tissue and varies according to the type of surgery performed. Common side effects may include but are not limited to pain, fatigue, swelling, numbness, and risk of infection.

How long does immunotherapy last?

Cancer immunotherapy offers the possibility for long-term control of cancer.

Immunotherapy can “train” the immune system to remember cancer cells. This “immunomemory” may result in longer-lasting and potentially permanent protection against cancer recurrence.

Clinical studies on long-term overall survival have shown that the beneficial responses to cancer immunotherapy treatment can be durable—that is, they continue even after treatment is completed.

How long has immunotherapy been used as a cancer treatment?

Cancer immunotherapy originated in the late 1890s with a cancer surgeon named Dr. William B. Coley (1862–1936) . He discovered that infecting cancer patients with certain bacteria sometimes resulted in tumor regression and even some complete remissions. Advances in cancer immunology since Coley’s time have revealed that, in patients that responded to his treatment, his bacterial toxin therapy stimulated their immune systems to attack the tumors.

While Coley’s approach was largely dismissed during his lifetime, his daughter, Helen Coley Nauts , discovered his old notebooks and founded the Cancer Research Institute in 1953 to support research into his theory. In 1990, the FDA approved the first cancer immunotherapy, a bacteria-based tuberculosis vaccine called Bacillus Calmette-Guérin (BCG), which was shown to be effective for patients with bladder cancer .

What is the relationship between cancer and the immune system?

While many of our cells grow and divide naturally, this behavior is tightly controlled by a variety of factors, including the genes within cells. When no more growth is needed, cells are told to stop growing.

Unfortunately, cancer cells acquire defects that cause them to ignore these stop signals, and they grow out of control. Because cancer cells grow and behave in abnormal ways, this can make them stand out to the immune system, which can recognize and eliminate cancer cells through a process called immunosurveillance .

However, this process isn’t always successful. Sometimes cancer cells develop ways to evade and escape the immune system, which allows them to continue to grow and metastasize, or spread to other organs. Therefore, immunotherapies are designed to boost or enhance the cancer-fighting capabilities of immune cells and tip the scales in the immune system’s favor.

What types of immunotherapy treatments are there?

Immunotherapy treatments can be broken down into five types:

• Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers (known as antigens) on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Some targeted antibody-based immunotherapies, known as antibody-drug conjugates (ADCs), are equipped with anti-cancer drugs that they can deliver to tumors. Others, called bi-specific T cell-engaging antibodies (BiTEs), bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. All targeted antibody therapies are currently based on monoclonal antibodies (clones of a parent bonding to the same marker(s)).
• Adoptive cell therapy takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, cancer-fighting T cells are modified and equipped with specialized cancer-targeting receptors known as CARs (chimeric antigen receptors) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor-infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients.
• Oncolytic virus therapy uses viruses that are often, but not always, modified in order to infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body.
• Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Some versions are engineered to produce immune-stimulating molecules. Preventive cancer vaccines inoculate individuals against cancer-causing viruses and bacteria, such as HPV or hepatitis B.
• Immunomodulators govern the activity of other elements of the immune system to unleash new or enhance existing immune responses against cancer. Some, known as antagonists, work by blocking pathways that suppress immune cells. Others, known as agonists, work by stimulating pathways that activate immune cells. Checkpoint inhibitors target the molecules on either immune or cancer cells, telling them when to start or stop attacking a cancer cell. Cytokines are messenger molecules that regulate maturation, growth, and responsiveness. Interferons (IFN) are a type of cytokine that disrupts the division of cancer cells and slows tumor growth. Interleukins (IL) are cytokines that help immune cells grow and divide more quickly. Adjuvants are immune system agents that can stimulate pathways to provide longer protection or produce more antibodies (they are often used in vaccines, but may also be used alone).

What is the difference between immunotherapy and chemotherapy?

Chemotherapy is a direct form of attack on rapidly-dividing cancer cells, but this can affect other rapidly dividing cells including normal cells. When patients respond, the treatment’s effects happen immediately. These direct effects of chemotherapy, however, last only as long as treatment continues.

Immunotherapy treats the patient’s immune system, activating a stronger immune response or teaching the immune system how to recognize and destroy cancer cells. Immunotherapy may take more time to have an effect, but those effects can persist long after treatment ceases.

Who can receive immunotherapy? What immunotherapies are approved for standard care?

As of March 2022, the U.S. Food and Drug Administration had approved over 60 immunotherapies that together cover almost every major cancer type:

• Aldesleukin (immunomodulator) for kidney cancer and melanoma
• Alemtuzumab (targeted antibody) for leukemia
• Amivantamab (bispecific antibody) for lung cancer
• Atezolizumab (checkpoint inhibitor) for bladder, liver, and lung cancer, and melanoma
• Avelumab (checkpoint inhibitor) for bladder, kidney, and skin cancer (Merkel cell carcinoma)
• Axicabtagene ciloleucel (CAR T cell therapy) for lymphoma
• Bacillus Calmette-Guérin [BCG] (vaccine) for bladder cancer
• Belantamab mafodotin-blmf (antibody-drug conjugate) for multiple myeloma
• Bevacizumab (targeted antibody) for brain, cervical, colorectal, kidney, liver, lung, and ovarian cancer
• Blinatumomab (bi-specific T cell-engaging antibody) for leukemia
• Brentuximab vedotin (antibody-drug conjugate) for lymphoma
• Brexucabtagene autoleucel (CAR T cell therapy) for leukemia and lymphoma
• Cemiplimab (checkpoint inhibitor) for lung cancer and skin cancer (basal cell carcinoma and cutaneous squamous cell carcinoma)
• Cetuximab (targeted antibody) for colorectal and head and neck cancer
• Ciltacabtagene autoleucel (CAR T cell therapy) for multiple myeloma
• Daratumumab (targeted antibody) for multiple myeloma
• Denosumab (targeted antibody) for sarcoma
• Dinutuximab (targeted antibody) for pediatric neuroblastoma
• Dostarlimab (checkpoint inhibitor) for uterine (endometrial) cancer
• Durvalumab (checkpoint inhibitor) for lung cancer
• Elotuzumab (targeted antibody) for multiple myeloma
• Enfortumab vedotin-ejfv (antibody-drug conjugate) for bladder cancer
• Gemtuzumab ozogamicin (antibody-drug conjugate) for leukemia
• Granulocyte-macrophage colony-stimulating factor, or GM-CSF (immunomodulator) for neuroblastoma
• Hepatitis B Vaccine (Recombinant) (preventive vaccine) for liver cancer
• Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant (preventive vaccine) for cervical, vulvar, vaginal, and anal cancer
• Human Papillomavirus 9-valent Vaccine, Recombinant (preventive vaccine) for cervical, vulvar, vaginal, anal, and throat cancer
• Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant (preventive vaccine) for cervical cancer
• Ibritumomab tiuxetan (antibody-drug conjugate) for lymphoma
• Idecabtagene vicleucel (CAR T cell therapy) for multiple myeloma
• Imiquimod (immunomodulator) for skin cancer (basal cell carcinoma)
• Inotuzumab ozogamicin (antibody-drug conjugate) for leukemia
• Interferon alfa-2a (immunomodulator) for leukemia and sarcoma
• Interferon alfa-2b (immunomodulator) for leukemia, lymphoma, and melanoma
• Ipilimumab (checkpoint inhibitor) for colorectal, liver, and lung cancer, and melanoma and mesothelioma
• Isatuximab (targeted antibody) for multiple myeloma
• Lisocabtagene maraleucel (CAR T cell therapy) for lymphoma
• Loncastuximab tesirine​ (antibody-drug conjugate) for lymphoma
• Margetuximab (targeted antibody) for breast cancer
• Mogamulizumab (targeted antibody) for lymphoma
• Naxitamab-gqgk (targeted antibody) for neuroblastoma
• Necitumumab (targeted antibody) for lung cancer
• Nivolumab (checkpoint inhibitor) for bladder, colorectal, esophageal, GEJ, head and neck, kidney, liver, lung, and stomach cancer, lymphoma, melanoma, and mesothelioma
• Obinutuzumab (targeted antibody) for leukemia and lymphoma
• Ofatumumab (targeted antibody) for leukemia
• Panitumumab (targeted antibody) for colorectal cancer
• Peginterferon alfa-2b (immunomodulator) for melanoma
• Pembrolizumab (checkpoint inhibitor) for bladder, breast, cervical, colorectal, esophageal, head and neck, kidney, liver, stomach, lung, and uterine cancer as well as lymphoma, melanoma, and any MSI-H or TMB-H solid cancer regardless of origin
• Pertuzumab (targeted antibody) for breast cancer
• Pexidartinib (immunomodulator) for tenosynovial giant cell tumor
• Polatuzumab vedotin (antibody-drug conjugate) for lymphoma
• Poly ICLC (immunomodulator) for skin cancer (squamous cell carcinoma)
• Ramucirumab (targeted antibody) for colorectal, esophageal, liver, lung, and stomach cancer
• Relatlimab (checkpoint inhibitor) for melanoma
• Rituximab (targeted antibody) for leukemia and lymphoma
• Sacituzumab govitecan-hziy (antibody-drug conjugate) for bladder and breast cancer
• Sipuleucel-T (vaccine) for prostate cancer
• Tafasitamab (targeted antibody) for lymphoma
• Tebentafusp-tebn (bispecific antibody) for melanoma
• Tisagenlecleucel (CAR T cell therapy) for leukemia (including pediatric) and lymphoma
• Tisotumab vedotin (antibody-drug conjugate) for cervical cancer
• Trastuzumab (targeted antibody) for breast, esophageal, and stomach cancer
• Trastuzumab deruxtecan (antibody-drug conjugate) for breast, esophageal, and stomach cancer
• Trastuzumab emtansine (antibody-drug conjugate) for breast cancer
• T-VEC (oncolytic virus) for melanoma

New immunotherapies are being developed and immunotherapy clinical trials are under way in nearly all forms of cancer.

Can people with autoimmune diseases and cancer be treated with immunotherapy?

People with mild autoimmune diseases are able to receive most immunotherapies . Typically, autoimmune treatment is adjusted and a checkpoint immunotherapy, such as those targeting the PD-1/PD-L1 pathway, is used. However, each patient should speak with his or her doctor regarding the options that are most appropriate.

Can people with HIV be treated with immunotherapy?

People with HIV who are receiving effective anti-viral treatment and whose immune systems are functioning normally may respond to cancer immunotherapy and are therefore eligible to receive immunotherapy, both as a standard of care and as part of a clinical trial.

How can I receive immunotherapy treatment?

The administration and frequency of immunotherapy regimens vary according to the cancer, drug, and treatment plan. Clinical trials can offer many valuable treatment opportunities for patients. Discuss your clinical trial options with your doctor.

How can I tell whether immunotherapy is working?

Immunotherapy treatments may take longer to produce detectable signs of tumor shrinkage compared to traditional therapies. Sometimes tumors may appear to grow on scans before getting smaller, but this apparent swelling may be caused by immune cells infiltrating and attacking the cancer. Many patients who experience this phenomenon, known as pseudoprogression, often report feeling better overall.

In certain cancer types, immune-related side effects may be linked with treatment success—specifically, melanoma patients who develop vitiligo (blotched loss of skin color)—but for the vast majority of patients, no definitive link has been established between side effects and immunotherapy’s effectiveness.

How is the Cancer Research Institute involved in the development of immunotherapy?

For more than 65 years , the Cancer Research Institute (CRI) has been the pioneer in advancing immune-based treatment strategies against cancer. It is the world’s leading nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all types of cancer.

CRI provides financial support to scientists at all stages of their careers along the entire spectrum of immunotherapy research and development: from basic discoveries in the lab that shed light on the fundamental components and mechanisms of the immune system and its relationship to cancer, to efforts focused on translating those discoveries into lifesaving treatments that are then tested in clinical trials for cancer patients.

What is cancer immunology?

Cancer immunology studies the relationship between cancer and the body’s immune system, including its innate ability to prevent or eliminate cancer cells, called immunosurveillance. Research shows that the body’s natural defense mechanisms can recognize and target cancer cells. Cancer immunologists focus on developing immunotherapies to boost those natural defenses.

What are immunotherapies?

Cancer immunotherapies also are known as biologic therapy, biotherapy, or biological response modifier therapy, and include checkpoint blockade, cancer vaccines, monoclonal antibodies, oncolytic virus therapy, T cell transfer, and other immune-modulating drugs such as cytokines and other adjuvant therapies. These effective ways for preventing, managing, or treating different cancers can be used in conjunction with surgery, chemotherapy, or radiation.

Is cancer immunology a new field of research?

The earliest forms of what would later be considered the start of cancer immunotherapy originated with research done by Dr. William B. Coley (1862-1936), a cancer surgeon and father of CRI founder Helen Coley Nauts . He discovered that “killed” bacteria stimulated the immune system to attack cancer cells. Modern cancer immunology is based on more recent advances in scientific understanding of the immune system’s various components, their function, and their role in cancer control. Cancer immunology is a relatively young field, but advances in treatment are aided by donor support.

Where can I get more information about immunology?

• Read our timeline of milestones in the field.
• Learn what immunotherapy is .
• Discover which immunotherapies are available for different cancers .
• Find out how different types of immunotherapy work .
• Get to know the scientists and patients behind the progress .
• Search for patient-specific resources .

Boosting the Body’s Immune System to Fight Cancer

Immunotherapy treatment harnesses the body’s natural strength to fight cancer—empowering the immune system to conquer more types of cancer and save more lives.

bind to antigens on threats in the body (e.g., bacteria, viruses, cancer cells) and mark cells for attack and destruction by other immune cells

release antibodies to defend against threats in the body

CD4+ Helper T Cells

send “help” signals to the other immune cells (e.g., B cells and CD8+ killer T cells) to make them more efficient at destroying harmful invaders

CD8+ Killer T Cells

destroy thousands of virus-infected cells each day, and are also able to seek out and destroy cancer cells

help immune cells communicate with each other to coordinate the right immune response

Dendritic Cells

digest foreign and cancerous cells and present their proteins to immune cells that can destroy them

Macrophages

engulf and destroy bacteria, virus-infected cells, and cancer as well as present antigens to other immune cells

Natural Killer Cells

recognize and destroy virus-infected and tumor cells quickly without the help of antibodies and “remember” these threats

Regulatory T Cells

provide the checks and balances to ensure that the immune system does not overreact

How the Immune System Works

Organs, tissues, and glands around your body coordinate the creation, education, and storage of key elements in your immune systems.

Thin tube about 4 to 6 inches long in the lower right abdomen. The exact function is unknown; one theory is that it acts as a storage site for “good” digestive bacteria

Bone marrow

Soft, sponge-like material found inside bones. Contains immature cells that divide to form more blood-forming stem cells, or mature into red blood cells, white blood cells (B cells and T cells), and platelets

Cells lining this set of organs and glands, as well as the bacteria throughout it, influence the balance of the immune system.

Lymph nodes

Small glands located throughout the body that filter bacteria, viruses, and cancer cells, which are then destroyed by special white blood cells. Also, the site where T cells are “educated” to destroy harmful invaders in your body

This organ’s receptors detect bacteria and viruses. Nasal mucus catches these pathogens so the immune system can learn to defend against them.

This organ is not only a physical barrier against infection but also contains dendritic cells for teaching the rest of the body about new threats. The skin microbiome is also an important influence the balance of the immune system.

An organ located to the left of the stomach. Filters blood and provides storage for platelets and white blood cells. Also serves as a site where key immune cells (B cells) multiply in order to fight harmful invaders

A set of organs that can stop germs from entering the body through the mouth or the nose. They also contain a lot of white blood cells.

Thymus gland

Small gland situated in the upper chest beneath the breastbone. Functions as the site where key immune cells (T cells) mature into cells that can fight infection and cancer

Immunotherapy Matters, For One and All

As a science-first organization dedicated to supporting cancer immunotherapy research, we’re funding a future that fights back against cancer—all with your help.

of every dollar spent goes to programs

All cancers

can potentially be treated with immunotherapy

clinical trials funded

$28.5 Million

awarded in 2021

News & Events

AACR 2022 Recap: T Cells Still On Top, But Make Room for Myeloid Cells

#Immune2Cancer Day 2022

On Friday, June 10, 2022, we invite you to raise awareness of the lifesaving potential of immunotherapy.

Giving Tuesday 2022

Be a part of the global generosity movement and celebrate all acts of giving. #GivingTuesday

Bring to Life More Cures, Together

Become part of CRI’s mission to create a world immune to cancer

This website uses tracking technologies, such as cookies, to provide a better user experience. If you continue to use this site, then you acknowledge our use of tracking technologies. For additional information, review our Privacy Policy .

Together we are beating cancer

• Cancer types
• Breast cancer
• Bowel cancer
• Lung cancer
• Prostate cancer
• Cancers in general
• Clinical trials
• Causes of cancer
• Coping with cancer
• Managing symptoms and side effects
• Mental health and cancer
• Money and travel
• Death and dying
• Cancer Chat forum
• Health Professionals
• Cancer Statistics
• Cancer Screening
• Learning and Support
• NICE suspected cancer referral guidelines
• Make a donation
• By cancer type
• Leave a legacy gift
• Donate in Memory
• Find an event
• Race for Life
• Charity runs
• Charity walks
• Search events
• Relay for Life
• Volunteer in our shops
• Help at an event
• Help us raise money
• Campaign for us
• Do your own fundraising
• Fundraising ideas
• Get a fundraising pack
• Return fundraising money
• Fundraise by cancer type
• Set up a Cancer Research UK Giving Page
• Find a shop or superstore
• Become a partner
• Cancer Research UK for Children & Young People
• Our Play Your Part campaign
• Brain tumours
• Skin cancer
• All cancer types
• By cancer topic
• New treatments
• Cancer biology
• Cancer drugs
• All cancer subjects
• All locations
• By Researcher
• Professor Duncan Baird
• Professor Fran Balkwill
• Professor Andrew Biankin
• See all researchers
• Our achievements timeline
• Our research strategy
• Involving animals in research
• Research opportunities
• For discovery researchers
• For clinical researchers
• For population researchers
• In drug discovery & development
• In early detection & diagnosis
• For students & postdocs
• Our funding schemes
• Career Development Fellowship
• Discovery Programme Awards
• Clinical Trial Award
• Biology to Prevention Award
• View all schemes and deadlines
• Applying for funding
• Start your application online
• How to make a successful applicant
• Funding committees
• Successful applicant case studies
• How we deliver research
• Our research infrastructure
• Events and conferences
• Our research partnerships
• Facts & figures about our funding
• Develop your research career
• Recently funded awards
• Manage your research grant
• Notify us of new publications
• Find a shop
• Volunteer in a shop
• Donate goods to a shop
• Our superstores
• Shop online
• Wedding favours
• Cancer Care
• Flower Shop
• Our eBay store
• Shoes and boots
• Bags and purses
• We beat cancer
• We fundraise
• We develop policy
• Our global role
• Our organisation
• Our strategy
• Our Trustees
• CEO and Executive Board
• How we spend your money
• Early careers
• Your development

Cancer News

• For Researchers
• For Supporters
• Press office
• Publications
• Update your contact preferences
• About cancer
• Get involved
• Our research
• Funding for researchers

The latest news, analysis and opinion from Cancer Research UK

• Science & Technology
• Health & Medicine
• Personal Stories
• Policy & Insight
• Charity News
• Health & Medicine

Cancer waiting times: Latest updates and analysis

8 August 2024

This article provides information on the latest performance against cancer waiting times targets. We have another piece explaining the recent changes to cancer waiting times in England .

Over the past few years, pressure on NHS cancer services has been mounting.

Cancer waiting times, which show whether the health system is meeting its targets for quickly diagnosing and treating cancer, help show us the extent of this pressure.

Testing for cancer, diagnosing it and starting treatment quickly saves people from stress and anxiety. Not only this, but cancer that’s diagnosed and treated at an early stage, when it isn’t too large and hasn’t spread, is more likely to be treated successfully. Prompt diagnosis and treatment underpin this.

December 2023 was the first month that the reported data on cancer waiting times is reflecting the new updated NHSE targets , as explained in our previous article . 

The standards have been streamlined into 3 key cancer waiting time standards with associated targets that   indicate how well cancer services are doing .  

Here are the latest results in England for June 2024:

The Faster Diagnosis Standard:  Target Met

• 76.3% of people were diagnosed, or had cancer ruled out, within 28 days of an urgent referral in June 2024. The target is 75% and this target has only been met twice since its introduction in October 2021.

The 62-day referral to treatment standard: Target Missed

• Only 67.4% of people in England received their diagnosis and started their first treatment within 2 months (or 62 days) of an urgent referral* in June 2024. The target is 85% and has not been met since December 2015.

The 31-day decision to treat standard: Target Missed

• 90.9% of people started treatment** within 31 days of doctors deciding a treatment plan in June 2024. The target is 96% . 

The  above  data are specific to England. Scotland,  Wales and Northern Ireland also have their own cancer waiting times targets. 

The NHS in England is treating more patients than ever before, but today's figures show that in the first half of 2024, 30,200 cancer patients across England still had to wait longer than they should to begin their treatment. Even when people are treated on time, it’s a period of unimaginable stress for them and their loved ones, and delays that prolong this are unacceptable. The challenges facing the NHS are complex, and can’t be fixed overnight, but the UK government has a huge opportunity to tackle these problems. The Health and Social Care Secretary has committed to meet cancer waiting time standards by the end of this parliamentary term, and a dedicated long-term cancer strategy is vital in delivering on this promise.

What does this mean for people affected by cancer?

It can be easy to forget that behind these numbers are real people going through an incredibly anxious time.

Quantifying the impact of missing targets and longer waits on patient outcomes is difficult as the research is limited.

The picture is different for different cancer types – some progress quicker than others – but we know the overall impact is likely to be negative. One study estimated that a 4-week delay to cancer surgery  led to a 6-8% increased risk of dying .

People with more aggressive cancers are prioritised for early treatment where possible, but there can be good reasons why someone might experience a long wait for treatment.

For example, it can take longer to plan treatments intending to cure someone’s cancer, and sometimes patients need prehabilitation before starting treatment to give them the best chance of recovering well.

But increases in missed targets mean people who need potentially lifesaving cancer treatments are waiting, and worrying, for longer – and that is a big concern.

Despite delays, people shouldn’t put off coming forward if they are worried about symptoms. It’s always better to be on the waiting list than not at all, and if doctors are concerned, they will push things through as quickly as possible.

Getting back on track

Today’s cancer waiting times continue to show unacceptable waits for cancer patients in England and, despite the best efforts of NHS staff, a service under strain.   

Already this year, around 30,200 patients have waited longer than they should to begin treatment, and recent Cancer Research UK research showed that the proportion of patients waiting longer than 104 days to begin treatment has grown in recent years too.  

Behind every one of these missed targets are patients – along with their friends, family and loved ones – who are facing unacceptably long and anxious waits to find out if they have cancer and when they can begin treatment.  

But despite complex challenges facing cancer care, there’s a huge opportunity for the new government to turn things around. Positively, in their election manifesto , they have already promised to meet cancer wait targets, boost early diagnosis and improve survival.   

For the government to deliver on this commitment though, we need them to develop a dedicated, long-term strategy for cancer – a proper plan for improving cancer research and care. That strategy must set out the necessary investment needed in the cancer workforce, key NHS equipment and facilities, and in IT and digital systems. Alongside that, we also need the government to support the NHS to innovate and reform cancer services so that we can improve the quality and efficiency of cancer care.  

With cancer cases on the rise and improvements in survival showing signs of slowing , cancer is still the defining health issue of our time. That’s why we’re campaigning for the new UK Government to make this a turning point for cancer, and you can add your voice to the campaign here .   

* Urgent referrals include urgent referrals from a GP for cancer symptoms or breast symptoms, urgent referrals from a cancer screening programme, and referrals upgraded by a consultant.  

It’s important to note that the update to cancer waiting times standards in October 2023 means that more types of referral are now included in the 62-day standard. This means that that the 62-day standard now applies to more people than before.  

** This standa rd i ncludes people starting their first treatment for canc er and a lso people starting a ny subsequ ent treatments. B e fore October 2023, t h e 31 – day standard included first treatments only.  

I had half my bowel removed in 2019 due to colon cancer and was told all the cancer was taken away. In 2020, it returned to the bowel and spread to my spine, kidney and belly button and was told it was incurable. I had chemo and radiotherapy . Luckily, despite their predictions, I am still alive. I have just been told that the cancer on my bowel has grown. The team had a discussion then informed me that it had not grown enough to warrant treatment and that I’d been scanned for five years so should see my doctor in future. I am walking around with five tumours having two on the kidney which will eventually grow leaving me with little chance to get back in the system for treatment.

What the stats don’t tell you is, where the targets are missed, how much are they missed by. My urgent referral for prostate cancer was 11th March 24. I received my confirmed diagnosis of T2 with gleason score of 9 on 20th May following a biopsy. 70 days vs target of 28 days. I’m posting this on 1st July and as yet have no treatment plan, let alone been put on a waiting list. That’s 112 days vs target of 62 days for start of treatment from urgent referral. Either I’ve been very unlucky or the data you have for percentage of people meeting these targets is questionable.

Husband diagnosed with kidney cancer after a MRI for another reason. Dr referred for urgent review to urology after seeing the MRI he called for another reason. Was told by the urologist that a CT would be needed. This is what has happened next CT scan 20 Feb Results kidney cancer possibly Adrenal as primary and lung nodules so was referred to Endocrine.

Was told all above on the 27 Feb by phone call. Also being referred for a lung biopsy which we have heard nothing yet. March saw Endocrine team was told bloods were needed and urine test all done and results were back on the 20 th March.

21 March was told not Adrenal as the primary as previously thought it is kidney cancer still. Was told we would get a biopsy in two weeks time . I phoned up they said biopsy would be 24 April which is nearly 6/7 weeks after and well over the two week biopsy wait was told it would be. I am still chasing this up. Lung biopsy was told 4 week wait on the 27 Feb still no news. We have been passed from Kidney to Endcrine back to urology again. No treatment Not even seen an oncologist yet. Only had CT MRI Full blood Urine test One Doctor seen at one appointment Shocking really we was told on the the letter its stage 4 not even by a doctor.

I had a fall at work of about 9 feet. Sustained Multiple fractures, my Wrist, Collar bone. etc,. Had C.T Scan followed by M.I.R while in A&E. 5 days later got phone call to say they had found a growth. At Adrenal Gland was told it was on it.(So assumed on outside ) Then on the 6th day since fall got another phone call to go in for what the caller said was for emergency M.I.R and Bloods..In mean time received letter saying growth was inside the Adrenal Gland.? So do not know if on outside or inside and not told size of it..Just told When results of last M.I.R. are in system i would be getting appointment to Endocrinology. That was 3 weeks ago..I have phoned Endocrinology twice once it got to over 2 weeks. Keep being told my results are not yet in the System. And in any case waiting list for Endocrine appt,. is one huge long waiting list. Today weirdly i was told my results are still not in system but then was told She would get my Consultant i have not met yet to phone me..Obviously i cannot work until fractures heal and plaster comes off. So i have too much time to worry and feel in Limbo as to what will,… is to happen next..

Fourteen years of incompetent government.

too informative and thanks for sharing this much knowledge with us.

Husband diagnosed with bladder cancer in August 2023. Awaiting a bladder removal. Aggressive cancer & waiting list is 4-5 months. Due according to the surgeon to strikes. I will be taking legal advice & action. NOT good enough.

I had a PSA test in January that scored 19. The follow up test two weeks later scored 21. I then had an MRI scan followed buy a CT scan & prostate gland biopsy. On 19th May a consultant Urologist at Leicester General Hospital told me I had stage three cancer with a high Gleeson score. He prescribed hormone treatment and referred me to Oncology. On the 22nd Aug I saw an Oncology consultant & was told I needed seven & half weeks of radiotherapy. Owing to the “backlog” treatment wouldn’t start for two & half months and if I hadn’t heard anything by then to “Give them a call” I was advised by Prostaid to “chase this up” Today I called Radiotherapy at Leicester Royal Infirmary and was told I’m number eighty in the queue and the list is being cleared at four per week. Unfortunately, it looks as if I have another five months to wait before any futher treatment will start. I’ll continue with hormone injections.

My daughter was diagnosed with grade 4 bladder cancer on 14th July 2023. She has still not started treatment. Is this because they know she’s going to die so they see no urgency in treating her. They can’t operate and she only saw the oncologist 10 days ago. It’s disgraceful. She is very distressed at the lack of treatment and this can’t be doing her any good physically either.

I am not happy I have not had chemo for 6mths it is very stressful

From my own experience, I cannot fault the care and treatment I have received from Oxford University NHS Trust. I was referred by my GP for tests on 14/02/23, received a phone call from my local hospital, The Horton General in Banbury, on the 15th inviting me for a CT Scan on the 16th, on the 16th I received another phone call this time from the endoscopy unit offering me an appointment on the 18th,…. bad news! On the 1st March I was sat in front of my consultant at the Churchill Hospital in Oxford getting the really bad news. I started palliative chemotherapy and immunotherapy on 29th March and have just completed my sixth and final cycle of chemo with immuno to continue. Perhaps I am lucky (well only sort of, because the outcome is now per-ordained) because of where I live and OUHNHSTrust includes the Churchill Hospital, an acknowledged cancer care unit. Finally, a big shout out to ALL the wonderful and caring staff, from Professor Ramon De Melo, Dr. (Consultant) Paul Miller, all the Macmillan nurses, all the nurses and staff at the Horton GH in Banbury and particularly those at the Brodey Center who administer the chemo/immuno therapies.

I waited 10 weeks for results of my two yearly scan! Consultant said well if it was good news I would have rang you within a couple of weeks! I started palliative chemo 16 weeks after my scan! The stress this has caused for me and my family is unimaginable. My cancer is not curable but it is treatable. At the time of the scan my cancer spread was small but 16 weeks down the line who knows!

These figures showing the many missed targets are absolutely shocking but don’t come as a surprise. As a former experienced RadiationOncologist in the north of England, I kept making awareness of delays in cancer diagnosis and treatment, particularly radiotherapy, in the public domain 30 years ago. The current dreadful missed target figures are a direct result of long term significant underfunding of cancer services by many governments and are extremely worrying.

Tell us what you think

Leave a reply cancel reply.

Your email address will not be published. Required fields are marked *

Save my name, email, and website in this browser for the next time I comment.

Read our comment policy .

Highlighted content

Cancer vaccines - where are we, su2c gives £7.5m more to improve treatments for children’s and young people’s cancers, cancer waiting times: who are the long waiters , how secure data environments can help drive advances in health data research, 70 years of progress in cervical cancer research, an animal's guide to staying safe in the sun, related topics.

• Health service policy
• Treatments policy
• Cancer in the news

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• NEWS FEATURE
• 14 February 2024
• Correction 15 February 2024

The future of precision cancer therapy might be to try everything

• Elie Dolgin 0

Elie Dolgin is a science journalist in Somerville, Massachusetts.

You can also search for this author in PubMed   Google Scholar

Illustration: Shira Inbar

The blood cancer had returned, and Kevin Sander was running out of treatment options. A stem-cell transplant would offer the best chance for long-term survival, but to qualify for the procedure he would first need to reduce the extent of his tumour — a seemingly insurmountable goal, because successive treatments had all failed to keep the disease in check.

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

24,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 51 print issues and online access

185,98 € per year

only 3,65 € per issue

Rent or buy this article

Prices vary by article type

Prices may be subject to local taxes which are calculated during checkout

Nature 626 , 470-473 (2024)

doi: https://doi.org/10.1038/d41586-024-00392-2

Updates & Corrections

Correction 15 February 2024 : An earlier version of this feature stated that Philipp Staber’s lab uses a 386-well plate.

Kornauth, C. et al. Cancer Discov. 12 , 372–387 (2022).

Article   PubMed   Google Scholar  

Snijder, B. et al. Lancet Haematol. 4 , e595–e606 (2017).

O’Dwyer, P. J. et al. Nature Med. 29 , 1349–1357 (2023).

Malani, D. et al. Cancer Discov. 12 , 388–401 (2022).

Ranjan, T. et al. Cell Rep. Med. 4 , 101025 (2023).

Ranjan, T. et al. Neurooncol Adv. 5 , vdad055 (2023).

PubMed   Google Scholar  

Manzano-Muñoz, A. et al. npj Precis. Oncol. 6 , 90 (2022).

Mayoh, C. et al. Cancer Res. 83 , 2716–2732 (2023).

Al-Aloosi, M. et al. Front. Oncol. 13 , 1267650 (2024).

Gray, H. J. et al. npj Precis. Oncol. 7 , 45 (2023).

Bangi, E. et al. iScience 24 , 102212 (2021).

Bangi, E. et al. Sci. Adv. 5 , eaav6528 (2019).

Tsai, L. L. et al. Ann. Surg. 277 , e1143–e1149 (2023).

Peruzzi, P. et al. Sci. Transl. Med. 15 , eadi0069 (2023).

Download references

Reprints and permissions

Related Articles

• Medical research

Neuronal substance P drives metastasis through an extracellular RNA–TLR7 axis

Article 07 AUG 24

Glycosphingolipid synthesis mediates immune evasion in KRAS-driven cancer

The genomic landscape of 2,023 colorectal cancers

Engineered brain parasite ferries useful proteins into neurons

Research Highlight 07 AUG 24

Blood tests could soon predict your risk of Alzheimer’s

News Feature 07 AUG 24

Breast-cancer cells enlist nerves to spread throughout the body

News 07 AUG 24

Recruitment of Talent Positions at Shengjing Hospital of China Medical University

Call for top experts and scholars in the field of science and technology.

Shenyang, Liaoning, China

Shengjing Hospital of China Medical University

The Recruitment of Fuyao University of Science and Technology

This recruitment of Fuyao University Technologyof Science andUcovers 7 departments including the 6 Schools and the Faculty of Fundamental Disciplines.

Fuzhou, Fujian (CN)

Fuzhou FuYao Institute for Advanced Study

Educational Consultant

You will build and maintain strong relationships with local representatives, key distributors, schools, Ministries of Education, etc.

Riyadh - hybrid working model

Springer Nature Ltd

Senior Marketing Manager – Journal Awareness

Job Title: Senior Marketing Manager – Journal Awareness Location(s): London, UK - Hybrid Working Model Closing date: 25th August 2024             A...

London (Central), London (Greater) (GB)

Faculty Positions& Postdoctoral Research Fellow, School of Optical and Electronic Information, HUST

Job Opportunities: Leading talents, young talents, overseas outstanding young scholars, postdoctoral researchers.

Wuhan, Hubei, China

School of Optical and Electronic Information, Huazhong University of Science and Technology

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

• Alzheimer's disease & dementia
• Arthritis & Rheumatism
• Attention deficit disorders
• Autism spectrum disorders
• Biomedical technology
• Diseases, Conditions, Syndromes
• Endocrinology & Metabolism
• Gastroenterology
• Gerontology & Geriatrics
• Health informatics
• Inflammatory disorders
• Medical economics
• Medical research
• Medications
• Neuroscience
• Obstetrics & gynaecology
• Oncology & Cancer
• Ophthalmology
• Overweight & Obesity
• Parkinson's & Movement disorders
• Psychology & Psychiatry
• Radiology & Imaging
• Sleep disorders
• Sports medicine & Kinesiology
• Vaccination
• Breast cancer
• Cardiovascular disease
• Chronic obstructive pulmonary disease
• Colon cancer
• Coronary artery disease
• Heart attack
• Heart disease
• High blood pressure
• Kidney disease
• Lung cancer
• Multiple sclerosis
• Myocardial infarction
• Ovarian cancer
• Post traumatic stress disorder
• Rheumatoid arthritis
• Schizophrenia
• Skin cancer
• Type 2 diabetes
• Full List »

share this!

August 8, 2024

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

trusted source

Lifestyle habits can alleviate the effects of cancer treatment in children

by Béatrice St-Cyr-Leroux, University of Montreal

Over the past 30 years, the success rate of pediatric cancer treatments has improved dramatically. It is now above 80%—and even higher for some cancers.

While the reduction in mortality is heartening, there's a downside: about two-thirds of children who survive cancer will later suffer adverse effects from the aggressive treatments they received at a young age.

Cancer treatments can cause damage to growing bodies, including neurocognitive, endocrine and cardiometabolic complications such as dyslipidemia, hypertension and prediabetes.

To alleviate these effects, several years ago a multidisciplinary research team at Sainte-Justine children's hospital in Montreal—including Valérie Marcil, a professor in the Department of Nutrition at Université de Montréal—launched an initiative called Projet VIE.

The project has proven successful and is being extended this summer to all university hospitals in Quebec that treat children with cancer: CHU de Québec-Université Laval, CHU de Sherbrooke and the Montreal Children's Hospital.

Intervening as soon as possible

Projet VIE and its Quebec-wide version, Projet VIE-Québec, promote healthy lifestyle habits (nutrition, physical activity and mental health ) to mitigate the effects of cancer during and after treatment.

"The aim is to promote the well-being of children and teens with cancer," Marcil said. "We intervene as soon as possible after diagnosis because the treatments quickly cause changes" such as digestive complications and the ability to properly taste food.

Projet VIE has nutritionists who provide personalized follow-up and lead cooking workshops to encourage children and their families to eat a balanced diet , help them discover new foods and make eating an enjoyable experience again.

Patients and their families also receive psychological counseling and participate in physical activities, since exercise has protective effects on many of the body's systems.

'They've regained their confidence'

Young people who take part in Projet VIE along with their families appreciate the support provided by the program, Marcil said.

"Many children with cancer feel a loss of control over their bodies and develop a negative self-image. With this more comprehensive approach, they tell us they've regained the confidence to be physically active and rediscovered the joy of eating."

Marcil believes promoting a healthy lifestyle will also yield long-term benefits, particularly for cardiometabolic health, and she'll be studying this hypothesis in the coming years.

Explore further

Feedback to editors

US health regulator rejects MDMA treatment for PTSD, for now

Aug 10, 2024

Study finds baked potatoes can improve heart health for diabetics

Aug 9, 2024

National study shows how internal medicine chief residency has changed over 20 years

Vegan diet better than Mediterranean, finds new research

Memory problems in old age linked to a key enzyme, study in mice finds

Key factor found in drug-context links, relapse

Researchers outline promises, challenges of understanding AI for biological discovery

The dengue vaccine is effective and safe: Confirmation from the first global meta-analysis

'PTNM' system provides new classification for Peyronie's disease and penile curvature

Researchers crack a key celiac mystery: Where the gluten reaction begins

Related stories, precision medicine for pediatric cancers: new hope for children and adolescents.

Apr 29, 2019

When do Quebec doctors recommend exercise?

Jun 14, 2024

Report: Canada should ban all unhealthy food marketing that may be seen by children

Mar 20, 2024

Study: Preventing type 2 diabetes in young people is possible without medication

Mar 14, 2023

Rebooting healthy eating habits in child cancer survivors

Jul 13, 2020

How play can help break the cycle of violence

Feb 7, 2024

Recommended for you

Epigenetic change to DNA associated with cancer risk in 'multi-omics' study

Feedback loop promotes cancer cells' adaption to molecular stress

Unmasking hidden potential: LMO4 enhances T cell cancer-fighting abilities

Cannabis use tied to head and neck cancer

Aug 8, 2024

Drug shows promise for treating brain tumors resulting from breast cancer, trial reports

Computer simulations clarify how breast cancer spreads

Let us know if there is a problem with our content.

Use this form if you have come across a typo, inaccuracy or would like to send an edit request for the content on this page. For general inquiries, please use our contact form . For general feedback, use the public comments section below (please adhere to guidelines ).

Please select the most appropriate category to facilitate processing of your request

Thank you for taking time to provide your feedback to the editors.

Your feedback is important to us. However, we do not guarantee individual replies due to the high volume of messages.

E-mail the story

Your email address is used only to let the recipient know who sent the email. Neither your address nor the recipient's address will be used for any other purpose. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form.

Newsletter sign up

Get weekly and/or daily updates delivered to your inbox. You can unsubscribe at any time and we'll never share your details to third parties.

More information Privacy policy

Donate and enjoy an ad-free experience

We keep our content available to everyone. Consider supporting Science X's mission by getting a premium account.

E-mail newsletter

Select "Patients / Caregivers / Public" or "Researchers / Professionals" to filter your results. To further refine your search, toggle appropriate sections on or off.

Cancer Research Catalyst The Official Blog of the American Association for Cancer Research

Home > Cancer Research Catalyst > Experts Forecast Cancer Research and Treatment Advances in 2021

Experts Forecast Cancer Research and Treatment Advances in 2021

2020 was filled with unexpected challenges for cancer research and patient care. As many of us shifted our lives online in the wake of the COVID-19 pandemic, cancer research was paused, clinical trials were put on hold, appointments were rescheduled, and conferences were canceled or reformatted. 

All this occurred amidst a global pandemic that has killed more than 1.9 million people worldwide, a plummeting economy with record unemployment levels, and a national reckoning with racism and racial disparities in all facets of society—including health care.  

But there was also progress.  

An unprecedented level of scientific collaboration and dissemination led to rapid research advances, culminating in the  authorization  of two vaccines against SARS-CoV-2 less than 12 months after the  first reported COVID-19 cases .  Twenty-one novel oncology drugs  were approved by the U.S. Food and Drug Administration (FDA) in 2020, including for difficult-to-treat cancers such as  triple-negative breast cancer  and  certain gastrointestinal stromal tumors . The first  liquid biopsy next-generation sequencing tests  were approved, the first-in-human trial of  off-the-shelf CAR T-cell therapy  was launched, and the first comprehensive  report  on cancer disparities was released by the AACR.  

With 2020 behind us, what might we expect from 2021? 

Each year, we  publish  predictions from prominent cancer researchers summarizing the key advances in cancer research and treatment we can expect to see in the new year.  

This year, we spoke with thought leaders on five timely subjects, including COVID-19, cancer disparities, cancer prevention, immunotherapy, and precision medicine. These researchers provided their thoughts on the greatest challenges and expectations for their respective fields in the upcoming year.  

COVID-19 and Cancer  

Antoni Ribas, MD, PhD, FAACR

“The pandemic is going to have lasting impacts on cancer research.”

As we begin the new year, it is apparent that the COVID-19 pandemic will continue to affect cancer research and patient care for the foreseeable future.  

President of the AACR and Chair of the  AACR COVID-19 and Cancer Task Force ,  Antoni Ribas, MD, PhD, FAACR , discussed the challenges that the cancer field will continue to face as the pandemic persists into 2021, as well as his perspectives on where the field is headed. 

Vaccinating patients with cancer  

One of the major accomplishments to expect in 2021 is widespread COVID-19 vaccination, which Ribas hopes will be a turning point for patients with cancer. “The pandemic has delayed cancer diagnoses, has limited access to care and lifesaving treatments, and has unevenly impacted already vulnerable populations,” said Ribas, professor of Medicine, Surgery, and Molecular and Medical Pharmacology at Jonsson Comprehensive Cancer Center, University of California, Los Angeles. “Moving forward, I hope that vaccination will allow us to return to the care that has saved so many lives from the pandemic of cancer, which includes early detection and access to effective treatments.” 

Due to the disproportionate risks that COVID-19 poses for patients with cancer, Ribas and the AACR COVID-19 and Cancer Task Force advocated for patients with cancer to be given priority vaccination in a recent  article  for the AACR journal  Cancer Discovery . 

Ribas expects that 2021 will also provide additional information about the effects of cancer on COVID-19 vaccination. An important question is whether cancer therapies that either suppress or boost the immune system will alter the efficacy of vaccination, Ribas explained. “The limited evidence we have does not suggest that cancer or cancer treatments have an effect on COVID-19 vaccines, but we need to complete additional trials in patients undergoing various therapies to determine their impact, if any, on the ability to mount a protective response to COVID-19.” 

Adapting cancer clinical trials     “The pandemic has led to the biggest change to clinical trials in the last 30 to 40 years,” said Ribas. He predicts that many of the changes will continue into 2021 and beyond due to the positive impacts they will likely have on increasing access to clinical trials in the future. 

Prior to the pandemic, clinical trials required numerous in-person visits, not only for receiving treatment, but also for completing paperwork and undergoing routine imaging and blood draws, Ribas explained. However, as medical facilities began to scale back operations last spring, clinical trials were quickly adapted to allow participants to continue their involvement without having to visit the clinic. Patients were able to provide consent remotely, utilize telemedicine for appointments, and receive oral medications and other treatments at home. For procedures that required in-person visits, such as imaging or blood tests, patients were able to visit local facilities rather than having to travel to distant research facilities.  

“The pandemic is going to have lasting impacts on cancer research. One benefit of the pandemic is that it has forced clinical researchers to determine which procedures are absolutely necessary to do in person and which can be completed remotely,” Ribas noted. Although he acknowledged that there has been reduced clinical trial enrollment during the COVID-19 pandemic, he expects that in the long run, “these changes will broaden the ability of people to participate in clinical trials, especially for patients who do not live near research centers and may otherwise not have the means to travel for multiple visits.”  

Supporting the cancer research workforce  

An important goal identified by Ribas for the upcoming year is supporting cancer research through the challenges brought on by the pandemic.  

“As the pandemic began, many of the activities that were considered the norm in cancer research had to be changed,” Ribas said, citing the cancellations or adaptations of scientific conferences as one key example. “The first large virtual conference in the field was the AACR Virtual Annual Meeting, which had to be organized within just a month without any road map for this type of meeting.” Twenty-five smaller conferences organized by the AACR were also converted to virtual meetings in 2020.  

“It was a big change for the organization and the broader scientific community, but it also provided an opportunity to embrace new technologies to reach more people and make the latest cancer research content available to people around the world,” Ribas noted.  

Looking ahead to 2021, Ribas anticipates that most conferences will remain virtual. “Once we reach the tipping point where enough people have been vaccinated to effectively prevent viral spread, we can start thinking about a timeline to resume in-person conferences where there are more opportunities for researchers to interact and collaborate, but there are going to be a lot of logistical factors to consider.”  

Ribas expects that the pandemic will continue to be particularly challenging for early-career investigators who are facing a lack of funding and job opportunities in the next year due to budgeting shortfalls at foundations, universities, and research institutions. Other pandemic-related challenges include reduced time in the lab to generate data and the inability to travel to job interviews or establish connections at in-person conferences. 

In light of these challenges, Ribas believes supporting early-career investigators should be a priority in 2021. He noted that the AACR COVID-19 and Cancer Task Force is examining ways to address these challenges, such as advocating to lawmakers to increase funding for cancer research. “There are a lot of things we need to act on in a short time,” he said. 

Ribas added that cancer research has not only helped improve treatments for cancer, but has also greatly benefited other research disciplines, including treatment and vaccine development for COVID-19. “The vaccines from Pfizer/BioNTech and Moderna were both developed using a platform that was initially conceived for cancer immunotherapy,” Ribas explained. “Because of cancer research, this technology was readily available to adapt for COVID-19 vaccination. It took only a month and a half from the time the virus was sequenced before the first patients were receiving COVID-19 vaccines in clinical trials.” Advances in cancer therapeutics have also benefited the treatment of COVID-19, as some of the drugs used in cancer treatment have shown to be effective for patients with COVID-19.  

“If we don’t step in and support cancer research through this time, there will be long-lasting consequences for the medical field at large,” he noted. 

Ribas is optimistic that the incoming presidential administration will be supportive in addressing the hurdles the cancer research community now faces. “In President-elect Biden and Vice President-elect Harris, we have two longstanding advocates of using science to make public policy and funding decisions,” he said, adding that both Biden and Harris have lost family members to cancer. “We’ve been set back so much by this pandemic, but I expect the new administration will partner with the cancer research community in alleviating some of the major problems that the field is facing now.” 

Predictions for COVID-19 and Cancer in 2021

– COVID-19 vaccinations for patients with cancer – Continued adaptations to cancer clinical trials – Support for the cancer research workforce

Cancer Disparities 

Lisa Newman, MD, MPH

“Cumulative stresses, such as exposure to racism and discrimination over a lifetime, can lead to epigenetic changes that may then affect risk for a variety of cancers.”

2020 brought us a new pandemic, but it also forced us to reckon with a very old plague—that of racial inequity. 

“Several cataclysmic events occurred over this past summer—the horrific murders of African Americans at the hands of law enforcement officers and the COVID-19 pandemic with its disproportionate impact on minorities—all forcing us to confront systemic racism and its effects on public health,” said surgeon and breast cancer researcher  Lisa Newman, MD, MPH , chief of Breast Surgery at New York-Presbyterian/Weill Cornell Medical Center. Newman is a member of the  AACR Minorities in Cancer Research Council . 

Disparities in health are  seen in cancer  as well, with minority populations, including African Americans, having  higher incidence and mortality rates  for many cancer types. Minorities are also more likely to be diagnosed with advanced and aggressive cancers and are  underrepresented  in clinical trials for cancer treatments.  

The biological and social factors that contribute to disparities in cancer incidence and mortality are under investigation. Newman discussed her predictions for where the cancer disparities field is headed in 2021. 

Identifying ancestral determinants of cancer risk  

Newman anticipates that one of the major focuses of the cancer disparities field in the next year will be studying how genetic ancestry impacts cancer incidence and treatment outcomes. Prior  work  has shown that Western sub-Saharan ancestry increases the risk of triple-negative breast cancer. This may account for the greater rates of this breast cancer subtype among African Americans, many of whom have Western sub-Saharan ancestry due to the colonial-era trans-Atlantic slave trade. Similarly, Indigenous American ancestry in Latina women has been shown to be  associated  with increased risk of HER2-positive breast cancer. According to Newman, identifying potentially actionable genetic determinants of ancestry-related breast cancer risk will be one key research direction in 2021. She noted that clinical trials are already  underway  to evaluate the utility of germline markers, including markers of ancestry, in personalized screening programs for breast cancer. 

“We are only beginning to appreciate the value of germline genetics in evaluating ancestry and the role that it plays in cancer risk,” said Newman. “I think we will be seeing a lot of similar research for other cancer types. This is a very exciting direction in cancer disparities research.” 

Determining the impact of allostatic load   

Newman also expects that the field will continue to study how allostatic load—the “wear and tear” on the body from stress—impacts cancer risk. “We’re learning that cumulative stresses, such as exposure to racism and discrimination over a lifetime, can lead to epigenetic changes that may then affect risk for a variety of cancers,” Newman said. Epigenetic changes can increase cancer risk through effects on the microbiome, among other mechanisms, she added.  

Newman explained that the higher rates of certain cancers in minority populations may be due, in part, to the biological changes that occur in response to the unique stresses they disproportionately face, such as racism and poverty. She anticipates that advances in 2021 will provide a deeper understanding of the biological consequences of stress in minority populations. 

Understanding social determinants of cancer disparities  

Another priority for the field in 2021 will be expanding knowledge about the social determinants of health and how they impact cancer risk, according to Newman. “We are just starting to scratch the surface in understanding how social determinants of health influence disparities in cancer risk and outcomes,” she said.  

Factors such as poverty and lack of health care access among minority populations can promote obesity and other comorbidities that increase cancer risk. As an example, the higher poverty rate among African Americans is associated with a higher proportion of African Americans living in food deserts with lower access to healthy dietary options, Newman explained. 

Newman anticipates that the COVID-19 pandemic and recession will exacerbate many existing cancer disparities due to the greater losses of jobs and health insurance experienced by minority populations. Furthermore, the hiatus in screening programs at the onset of the pandemic will likely lead to later diagnoses of cancer in communities that already suffer from more advanced stage distribution. “Minority populations with impaired access to screening programs are going to suffer disproportionately,” Newman said. 

She also cited the overwhelming impacts of the pandemic on safety-net hospitals, which are mostly found near minority communities and provide the majority of care for patients who lack health insurance. Newman explained that safety-net hospitals have more limited financial margins that have been devastated by the pandemic because of the high costs of critical care associated with COVID-19. “When safety-net hospitals try to return to somewhat normal practices after the pandemic, they are going to be much more behind financially in trying to provide cancer care and appropriate screening. This will end up disproportionately impacting minority populations,” Newman noted. 

Nevertheless, Newman is encouraged by the greater social awareness of racial inequities among the general public. “I think the American society has been awakened to the depths and tragedies of systemic racism and disparities in public health this year,” she said. “I hope this awareness will result in the expansion of much-needed research and investment in health equity initiatives to improve outcomes for communities that are socioeconomically disadvantaged.” 

Predictions for Cancer Disparities Research in 2021

– Identifying ancestral determinants of cancer risk – Determining the impact of allostatic load – Understanding social determinants of cancer disparities

Cancer Prevention and Early Detection 

Raymond DuBois, MD, PhD, FAACR

“The payoffs of cancer prevention are huge. I’m optimistic that we will see increased understanding and enthusiasm for this area of cancer research as we continue to learn more.”

While much of cancer research is focused on developing treatments for advanced cancers, a subset of the field aims to understand how to prevent cancer from occurring at all, as well as how to detect cancer earlier, when it is more easily treated. 

“The payoffs of cancer prevention are huge,” said  Raymond DuBois, MD, PhD, FAACR , who is Chair and President of the AACR Foundation and a Past President of the AACR. “I’m optimistic that we will see increased understanding and enthusiasm for this area of cancer research as we continue to learn more.” 

DuBois, also a professor and Dean of the College of Medicine at the Medical University of South Carolina and a member of the National Academy of Medicine, discussed his predictions for the cancer prevention field in 2021. 

The PreCancer Atlas: Characterizing premalignant changes  

What changes occur as normal tissue transitions to cancer? 

Can the changes found in premalignant tissues be targeted to prevent cancer from forming?   

To answer these questions, research groups from around the world have been working to generate a  PreCancer Atlas  with information about mutations and other early changes that occur at the molecular and cellular levels before and during cancer development. DuBois expects this to remain a major focus of the cancer prevention field in 2021 and a key long-term strategy for intercepting cancers at an early stage.  

“Characterizing premalignant changes will provide insight into the novel targets that may be present in this early phase of cancer development, as well as the pathways that are operative in the evolution to cancer,” he explained. “Understanding these changes will provide crucial information for developing new therapeutic approaches.”  

DuBois is particularly excited about the emerging evidence of changes in the type and density of immune cells in the premalignant microenvironment, which cause the premalignant lesions to become more resistant to the immune system. “I was surprised to learn that this immunosuppressive environment was established so early,” said DuBois, adding that this new information provides an opportunity to explore using vaccines or other interventions to inhibit immunosuppressive cells at an early stage to induce regression of premalignancies.   

“This story is still unfolding,” he said. “[This] year is going to be very exciting as publications come out showing the changes that are present in the premalignant tissue microenvironment, the potential vulnerabilities that exist in immune cells, and how we might target them in a nontoxic way to have a big impact.”  

Development of biomarkers and diagnostic tests   

Another area that DuBois expects the field to focus on in 2021 is the development and validation of biomarkers that would allow researchers to easily detect and monitor premalignant conditions. “It currently takes several months to years to conduct clinical trials examining disease progression and outcomes in patients with premalignant conditions,” said DuBois. “If we had validated biomarkers from premalignant lesions that could reliably indicate how patients were responding to clinical interventions, we could shorten the time and cost needed to conduct those trials.”  He noted that this approach has been successful in cardiovascular disease research, where high levels of low-density lipoprotein cholesterol serve as a biomarker for cardiovascular disease risk, allowing researchers to study the impact of investigational drugs on disease risk with a simple blood test. DuBois expects that findings from the PreCancer Atlas and other efforts will be key to identifying useful biomarkers for premalignancies.   

In addition, DuBois highlighted the need for accurate diagnostic tests to assess the risk of disease progression in individuals with premalignancies. “If we had a blood test that could distinguish between patients who were likely to develop a malignant cancer and those likely to develop a benign tumor, we could intervene early and appropriately for each population,” he explained. “We could limit the use of the more aggressive treatments to patients with a greater risk of malignant cancer and avoid those detrimental side effects in patients with lower risk.”  

Encouraging healthy behaviors and cancer screenings in the age of COVID-19   

A key element for cancer prevention is encouraging individuals to adopt healthy behaviors and undergo routine screenings. “It is estimated that 40 to 50 percent of cancers could be prevented if we could get everybody to follow all of the current recommendations for screening and healthy lifestyle behaviors,” said DuBois. “If we could do that successfully, it would be one of the biggest advances of our lifetime.”   

To reach this goal, understanding the reasons underlying unhealthy lifestyles will be critical. Many cancer-causing behaviors, such as smoking and poor diet, are rooted in addiction, so investing in behavioral and addiction science will be important to curbing these behaviors, DuBois explained. “We need to better understand the pathways in the brain that cause these addictions so that we can find more effective ways to intervene that are durable.”   

Identifying and addressing the obstacles to cancer screening will also be important. In 2021, a major hurdle will be the ongoing COVID-19 pandemic, which has already led to a dramatic decline in screening rates.  

“During the early stages of the pandemic, the last thing anyone wanted to do was go to a clinic and risk exposure, so people started putting off routine screenings,” said DuBois. “Now that we’ve realized that we’re going to be living with this virus for some time, we are trying to encourage patients to resume screenings.” Despite this encouragement, screening rates are still far below pre-pandemic levels. “That’s a huge problem, as it means many cancers may not be detected until it’s too late,” DuBois noted. Consistent with these concerns, an  editorial  by National Cancer Institute Director  Ned Sharpless, MD , predicted that there may be 10,000 additional deaths from breast and colorectal cancers over the next decade due to delays in screening caused by the pandemic.   

For patients who may be apprehensive about scheduling in-person appointments, DuBois recommends calling the clinic ahead of time to inquire about the safety precautions in place. “In my experience, many health care facilities have clearly defined procedures to help mitigate spread, such as social distancing, requiring masks, and decreasing the density in waiting rooms,” he explained. “Hearing about these has alleviated patient concerns to some degree, but I think this is going to continue to be a challenge until a vaccine is distributed widely.”   

Predictions for Cancer Prevention and Early Detection in 2021

– Characterization of premalignant changes

– Development of biomarkers and diagnostic tests

– Encouraging healthy behaviors and cancer screenings during COVID-19

Immunotherapy 

Marcela Maus, MD, PhD

“I’m hoping … the successful elimination of COVID-19 through vaccination will restore optimism and reverence for science and the immune system on a massive scale.”

“Due to the pandemic, there is a much greater appreciation of the immune system among the general public,” said  Marcela Maus, MD, PhD , director of the Cellular Immunology Program at Massachusetts General Hospital Cancer Center and associate professor of Medicine at Harvard Medical School  “I’m hoping this understanding and the successful elimination of COVID-19 through vaccination will restore optimism and reverence for science and the immune system on a massive scale.” 

Perhaps best known for its role in combatting viral and bacterial pathogens, the immune system is also able to respond to cancer cells, a function that has been utilized to treat patients with cancer. This class of cancer therapy—known as immunotherapy—encompasses several forms of treatment, all of which use a patient’s own immune system to target and eradicate their cancer. Immunotherapy has led to durable responses in many patients and has revolutionized cancer treatment over the last decade. 

“While vaccination for COVID-19 will be the major immunology achievement of 2021, I expect that immunotherapy will continue to drive increased responses and cures in patients with cancer as well,” Maus noted. 

Despite its many successes, immunotherapy does not benefit most patients and can be associated with  resistance  and severe side effects. Furthermore, the engineering of immune cells for certain forms of treatment requires time that many patients do not have. Maus discussed some of these challenges and the advances she expects to see in this field in 2021. 

New combinations for immune checkpoint inhibition  

Immune checkpoint inhibitors  help release the brakes on the immune system, allowing it to mount an antitumor response. This form of immunotherapy has led to dramatic and durable responses in some patients; however, the majority of tumors  do not respond  to this treatment, and many of the tumors that initially respond eventually develop  resistance .  

One strategy to improve the efficacy of immune checkpoint inhibitors is to  combine  them with other therapies. Maus expects to see new combination therapies emerge in 2021. “I think new combinations of immune checkpoint blockade with chemotherapy and immune agonists will continue to make inroads in the fight against solid tumors,” she said.  

Advances and challenges for adoptive cell therapy  

Adoptive cell therapy  (ACT) is a class of immunotherapy in which a patient’s T cells are extracted, engineered, multiplied, and reintroduced into the patient. ACT is effective for some hematologic malignancies, but it has not been successful for solid tumors. Maus anticipates that there will be advances in ACT for both hematologic malignancies and solid tumors in 2021. 

“In hematologic malignancies, I expect engineered T cells to be adopted more widely for patients with lymphoma, and perhaps move up a line or two of therapy,” she explained, adding that treating patients with ACT earlier would lower their exposure to chemotherapy and its long-term toxicities. Maus also predicts that new forms of engineered T cells could potentially become available, including idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) for the treatment of multiple myeloma.  

As far as solid tumors, Maus anticipates that publications in 2021 will demonstrate some efficacy for new therapies in development for solid tumors, but she expects that toxicity will likely be observed before durable responses. “I think any therapy that mediates antitumor responses in solid tumors will have some toxicity, but I think those side effects will be mitigated by medical interventions,” she said. Maus suggested that improving ACT for solid tumors may require combining it with other therapies or adding regulatory mechanisms to the engineered immune cells so that the response can be controlled to limit toxicity.  

A challenge that Maus believes the field needs to address in 2021 and beyond is expanding access to CAR T-cell therapy, a type of ACT. “Even though CAR T cells have achieved unprecedented efficacy in patients with lymphoma, they are still relatively underutilized due to the high cost, the high level of care and bespoke manufacturing required, and issues with health care infrastructure and payment models,” she explained. 

“Something here has to change,” Maus added. “All of the relevant stakeholders need to find a way to deliver on the promise of potentially curative cancer treatments for all patients.” 

Understanding mechanisms of resistance to immunotherapy  

Maus also predicts that the advent of new preclinical models in 2021 will bring about a greater understanding of the cellular pathways underlying resistance to immunotherapy. She explained that to date, most preclinical models of resistance have examined the role of just one cell type at a time; however, she expects to see the emergence of more comprehensive models in 2021 that will allow researchers to explore how different immune cells interact with each other and with the tumor. Additionally, Maus expects that single-cell technologies, such as transcriptional profiling, will enable researchers to better define the contributions of all immune cells, including the patient’s normal, non-engineered immune cells. These advances will also allow researchers to determine the impact of various interventions on immune function and immunotherapy resistance, Maus noted. 

“There has been a lot of focus on identifying mechanisms of resistance to CAR T-cell therapy and to immune checkpoint inhibition,” she said. “I’m optimistic that these will start to coalesce and lead to rational drug combinations to target resistance pathways and restore immune-mediated elimination of cancer.” 

Predictions for immunotherapy in 2021

– New combinations for immune checkpoint inhibition

– Advances for adoptive cell therapy for hematologic cancers and solid tumors 

– New preclinical models to study mechanisms of resistance 

Precision Medicine  

Keith Flaherty, MD

“Looking ahead to 2021, I’d say the use of biomarkers for PD-1/PD-L1-targeted therapies is going to finally bring us into the era of precision medicine.”

In its simplest definition, precision medicine aims to use a tumor’s molecular features to guide treatment, explained  Keith Flaherty, MD , professor of medicine at Harvard Medical School and Editor-in-chief of the AACR journal  Clinical Cancer Research .   

He noted that while basic precision medicine principles have been employed for some time, such as the traditional classification of breast cancer subtypes, the goal of truly precise and personalized cancer treatment has yet to be achieved. However, Flaherty is optimistic that the utilization of next-generation sequencing and large-scale data mining will bring the field significantly closer to this goal—particularly in the immunotherapy realm.  

More precise deployment of PD-1/PD-L1-targeted therapeutics  

While inhibitors of the PD-1/PD-L1 immune checkpoint have led to dramatic responses in many cancer types, only a  small portion  of patients experience a substantial benefit from these therapies. Identifying the molecular features beyond PD-L1 expression that determine which tumors are sensitive to these therapies—and using them to stratify patients for treatment—will be the primary direction of the precision medicine field in 2021, Flaherty predicted. 

“Looking ahead to 2021, I’d say the use of biomarkers for PD-1/PD-L1-targeted therapies is going to finally bring us into the era of precision medicine,” said Flaherty, noting that most other precision medicine strategies are in earlier stages of investigation. “I expect that we are going to see the adoption of positive selection biomarkers and—for the first time—the use of negative selection biomarkers in clinical trials to triage patients between different immunotherapy strategies,” he added.  

The use of liquid biopsy and circulating tumor DNA to detect and monitor such biomarkers has the potential to provide added depth and convenience compared to current methods; however, Flaherty expects that it will be some time before this approach is widely used. “Eventually, these technologies will begin to give us the information we need to analyze retrospective outcomes and identify whose tumors respond,” he explained. 

In addition to allowing more precise deployment of existing immune checkpoint inhibitors, Flaherty expects that understanding the molecular features that predict how tumors respond will facilitate the development of next-generation immunotherapies. “Once you understand which tumors are less likely to respond to PD-1/PD-L1-directed antibodies, you can then focus your efforts on developing new immunotherapies specifically for these types of tumors, thereby benefiting patient populations that do not respond to the current options.” 

Targeting fusion oncogenes  

The development of therapies to target fusion oncogenes is another direction that Flaherty expects the precision medicine field to explore in 2021 and beyond. “We have an increasing appreciation that tumors driven by fusion oncogenes are genetically simple,” he said. “If you can effectively target the fusion oncogene, you can achieve deep and durable clinical benefit.” 

A classic example of this approach is  BCR-ABL  targeting for the treatment of chronic myeloid leukemia. In recent years, therapies targeting  NTRK  or  RET  fusions have also been approved for the treatment of various cancers. Other fusion oncogenes that are emerging as potential therapeutic targets include FGFR fusions and BRAF fusions, according to Flaherty.  

“It’s becoming increasingly clear that fusion oncogenes may be the best type of mutation to target—better than point mutations—to achieve high response rates,” he added. “There will be some more successes in 2021, but in the next few years, we can probably expect to see a saturation of this area.” 

Targeting DNA damage response proteins  

Flaherty predicts that developing inhibitors that target proteins within the DNA damage response (DDR) will be another research direction in the upcoming years. “DNA repair proteins such as ATM, ATR, Chk1, and DNA polymerase-β are all subject to genetic alterations in cancer, providing potential therapeutic targets,” he explained.  

Flaherty noted that an extensive set of molecular features may define how a tumor responds to inhibitors of these proteins, similar to what has been observed for inhibitors of the DDR protein PARP. While PARP inhibitors are most effective in ovarian and breast cancers that have BRCA1 or BRCA2 mutations, they also show efficacy in cancers with other DNA repair deficiencies, as well as in some cancers with no apparent DDR deficiencies at all. Based on emerging clinical evidence, Flaherty expects similar observations to be seen with inhibitors of other DDR proteins. Identifying the molecular features that connote sensitivity to these drugs will be another major research focus of 2021 and beyond, Flaherty predicted. 

“We’re beginning to connect the dots between preclinical data about the molecular features found in tumors and their association with clinical responses to drugs targeting the DDR pathway,” said Flaherty. “In 2021, I think we will see mounting evidence that this class of drugs should become a part of standard therapy, admittedly with further research needed over the next few years.” 

Predictions for Precision Medicine in 2021

– More precise deployment of PD-1/PD-L1-targeted therapeutics

– Targeting fusion oncogenes

– Targeting DNA damage response proteins

• About This Blog
• Blog Policies
• Tips for Contributors

Interactive Timeline Celebrates History of the American Association for Cancer Research

Weighing Up the Cancer Problem

Use of Pembrolizumab Expanded to 13th Type of Cancer in Five Years

Cancel reply

Your email address will not be published. Required fields are marked *

Join the Discussion (max: 750 characters)...

This site uses Akismet to reduce spam. Learn how your comment data is processed .

• Healthcare Professionals Membership
• What Is Cancer Research
• Various Types of Cancer

There’s a powerful story behind every headline at Ohio State Health & Discovery. As one of the largest academic health centers and health sciences campuses in the nation, we are uniquely positioned with renowned experts covering all aspects of health, wellness, science, research and education. Ohio State Health & Discovery brings this expertise together to deliver today’s most important health news and the deeper story behind the most powerful topics that affect the health of people, animals, society and the world.  Like the science and discovery news you find here? You can support more innovations fueling advances across medicine, science, health and wellness by giving today.

BROUGHT TO YOU BY

• The Ohio State University
• College of Dentistry
• College of Medicine
• College of Nursing
• College of Optometry
• College of Pharmacy
• College of Public Health
• College of Veterinary Medicine
• Ohio State Wexner Medical Center
• Ohio State's Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute

Subscribe. The latest from Ohio State Health & Discovery delivered right to your inbox.

Reversing the side effects of immunotherapy cancer treatment

When immunotherapy triggers autoimmune and other side effects, a unique clinic is giving patients relief.

Contributing Writer Ohio State Wexner Medical Center

• Share on Facebook
• Share on Linkedin
• Share via Email
• Share this page

After months of breast cancer treatment, Julie Wullkotte was accustomed to enduring difficult side effects. But knowing her cancer cells were being destroyed was enough to keep her from complaining.

The burning sensation in her mouth was different.

Her mouth felt on fire whenever she ate anything other than the blandest foods. The slightest addition of garlic, onion or black pepper was like inhaling ghost peppers.

When she lost 15 pounds and complained the pain was affecting her quality of life, Wullkotte was referred to the Immunotherapy Management Clinic at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute ( OSUCCC – James ). The clinic is among the first of its kind in the United States, with a team of experts in rheumatology managing side effects of immunotherapy .

Wullkotte was diagnosed with a Sjögren’s-like syndrome, an autoimmune disease that’s a side effect of her immunotherapy drug. The same treatment that kept her cancer-free was also causing her immune system to attack itself.

With the help of Alexa Meara, MD , a rheumatologist at the OSUCCC – James, Wullkotte got better. “She knew exactly what it was and created a treatment plan to reverse the problem,” Wullkotte says.

Today, she hardly has symptoms. “I can eat Mexican food again, put pepper on my eggs in the morning and brush my teeth without screaming.”

Understanding immunotherapy and related side effects

Immunotherapy for cancer is a treatment that uses the body’s own natural defense systems to target and destroy cancer cells. Immunotherapy has quickly become the first line in treating many cancers. For these patients, cancer becomes more like a chronic disease that waxes and wanes.

A side effect of immunotherapy  is that the therapy can cause a patient’s immune system to go haywire. Immunotherapy’s side effects can occur at the time of treatment or even months or years later. Despite these adverse events, immunotherapy’s benefits outweigh the risks.

“You have a subset of patients with a purposely disordered immune system to keep the cancer at bay. However, all you need is some sort of other environmental stimulus, and now you have a new autoimmune disease,” Dr. Meara says.

The more common immunotherapy treatment becomes, the more Dr. Meara sees patients experiencing side effects.

Improving quality of life for cancer patients and survivors

Dr. Meara and her team achieve results people dream about when deciding to become a doctor, such as:

• A patient confined to a wheelchair from severe joint pain can walk again.
• A man with aggressive mouth sores can finally speak and swallow food and liquid again.
• A patient covered in skin rashes heals and regains quality of life.

Inflammation is a common side effect for patients with cancer treated by immunotherapy . As the treatment boosts the immune system to attack cancer cells, this heightened immune response can also target healthy tissues, causing inflammation .

Rheumatologists like Dr. Meara are trained to treat inflammation. “Most people think of rheumatic diseases as joint pain and rheumatoid arthritis, but there’s a whole world of autoimmune diseases that have nothing to do with joints,” Dr. Meara says.

For cancer patients who suffer from severe side effects of the immunotherapy drugs that kill cancer, Dr. Meara’s treatment can seem like a miracle. To Dr. Meara, it’s a matter of solving a puzzle. “I developed a reputation by figuring out the rarest of the rare diagnoses. And what’s more complicated than a patient with cancer and then weird autoimmune symptoms?” she says.

Giving immunotherapy patients their lives back

On any given day at the Immunotherapy Management Clinic, Dr. Meara and her team see everything from patients with joints so swollen they can’t walk to those experiencing skin rashes and sores. With the constraint of keeping the patient on the cancer medication, Dr. Meara’s goal is to determine what medication or lifestyle modification will reduce or cure a patient’s symptoms. Each case typically takes some trial and error, but the results can feel like a miracle to patients.

Kara Corps, DVM, PhD, an assistant professor in the Department of Veterinary Biosciences, received immunotherapy for her triple-negative breast cancer and developed rare side effects from the treatment. “I was declared cancer-free in December 2022, but my care is ongoing in the immunotherapy clinic to manage the side effects of the treatment that saved my life. I’m receiving extraordinary care that maintains my quality of life,” she says.

In the year since Mary Caldwell, APRN-CNP, joined the clinic as a nurse practitioner, she says it’s not unusual for patients to get back to feeling like their old selves after first coming to the clinic in wheelchairs due to pain or severe fatigue.

“They tell us they wish they would have found us earlier, but they’re so thankful we’re able to bring them back to their normal level of function,” Caldwell says.

Amanda Logsdon, RN, says Dr. Meara goes above and beyond to figure out the complexities of patients’ symptoms. “They often come here as a last-ditch effort and with significant depression because no one can help them,” Logsdon says.

With the clinic’s help, many patients’ lives are turned around. “It makes me feel so proud to be at her side to help accomplish these goals for the patient,” Logsdon says.

Opening doors to chronic disease research and care

Autoimmune diseases in general can be difficult to diagnose. The advent of immunotherapy means they’re showing up in cancer patients in new ways.

The challenge of treating rheumatology-oncology patients also presents opportunities. For example, Dr. Meara sees patients develop new disorders, like type 1 diabetes, nearly overnight. There are case reports of using some of the drugs designed for rheumatoid arthritis to reverse that. “If we can open the door to inflammation and type 1 diabetes, that could be a game changer,” Dr. Meara says.

As immunotherapy continues to cure more patients’ cancer, there’s still much to learn about how the therapy affects patients’ immune systems, says Dr. Meara. “I think oncology is changing the face of rheumatology and autoimmune diseases in a way that is fundamentally changing the immune system. There’s a whole new world out there, and I think that’s really exciting.”

Specialized treatment for immunotherapy side effects

The James Immunotherapy Management Clinic can help.

• Autoimmune Disease ,
• Cancer Care ,
• Immuno-Oncology ,
• Immunosuppressive ,
• Immunotherapy ,
• Immunotherapy Side Effects ,
• Immunotherapy Treatment ,
• OSUCCC – James

Related websites

• Ohio State's Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute

Articles on Health

Hitting the gravel to fuel cancer research at Pelotonia’s Gravel Day

By Steve Wartenberg

A gravel bike ride is raising money for cancer research at Ohio State as part of Pelotonia.

How to organize your medical records

By George Xanthopoulos, RHIA

When faced with a complex medical problem, organized medical records can help you stay focused on getting better. An Ohio State expert has tips.

Is menopause related to dementia?

By Jonathan Schaffir, MD

When are hiccups serious?

By J. Chad Hoyle, MD

Going bald too early?

By Kelly Tyler, MD

Get articles and stories about health, wellness, medicine, science and education delivered right to your inbox from the experts at Ohio State.

Required fields

By clicking "Subscribe" you agree to our Terms of Use . Learn more about how we use your information by reading our Privacy Policy .

An official website of the United States government

Here’s how you know

Official websites use .gov A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS A lock ( Lock A locked padlock ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Biden-Harris Administration Awards Nearly $9 Million to Improve Access to Cancer Screening and Connections to Follow-up Treatment in Underserved Communities to Deliver on Biden Cancer Moonshot Goals

Funding will leverage outreach specialists and patient navigators to conduct engagement in underserved communities to promote early cancer detection, connect people to screening services, and provide assistance accessing cancer care and treatment.

Today, to mark National Health Center Week, the U.S. Department of Health and Human Services (HHS), through the Health Resources and Services Administration (HRSA), awarded nearly $9 million to 18 HRSA-funded health centers to improve access to life-saving cancer screenings in underserved communities. Health centers will partner directly with National Cancer Institute-Designated Cancer Centers to expedite patient access to cancer care and treatment. These awards advance the Biden Cancer Moonshot mission to prevent 4 million cancer deaths by 2047 and end cancer as we know it. This effort builds on work supported by the 21st Century Cures Act to expand use of proven cancer prevention and early detection strategies to reduce cancer risk in all populations.

“HHS supports efforts to help people live longer, healthier lives. That’s why we are doing all we can to make cancer prevention and screening services accessible to all Americans,” said HHS Secretary Xavier Becerra. “The funding for health centers announced today is another step towards reducing health disparities across races, ethnicities, genders, and incomes—which is essential to realizing the President’s goal of ending cancer as we know it.”

Two years ago, President Biden and First Lady Jill Biden reignited the Cancer Moonshot and set two national goals: To decrease the cancer death rate by at least 50% over 25 years and to improve the experience of people who are touched by cancer.   The Biden-Harris Administration placed a strong emphasis on cancer screening, since Americans missed more than 10 million cancer screenings during the early days of the COVID-19 pandemic and patient outcomes are drastically improved with early detection.

“No matter where you live or what resources you have, everyone should be able to benefit from the tools we have to detect, diagnose and treat cancer before it’s too late,” said HRSA Administrator Carole Johnson. “HRSA is proud to increase our investment in partnerships between our health centers and cancer centers to improve access to live-saving cancer prevention in communities that have been underserved for too long.”

Cancer is the second-leading cause of death in the United States, with approximately 600,000 deaths annually. Appropriate screening and timely follow-up care help to detect cancer early and improve outcomes for patients. However, significant disparities in cancer screening and follow-up care persist, particularly among individuals of different income levels, insurance statuses, and racial or ethnic backgrounds.

Today’s awards build on HRSA’s previous investment of $11 million in 2023 and $5 million in 2022 announced as part of the Biden Cancer Moonshot.

HRSA’s Health Center Program is a cornerstone of our country’s health care system, especially for individuals and families who are uninsured, enrolled in Medicaid, living in rural or underserved areas, struggling to afford co-pays, experiencing homelessness, residing in public housing, or having difficulty finding a doctor or paying for care.

To locate a HRSA-supported health center, visit: https://findahealthcenter.hrsa.gov .

See the table below for a full list of the Fiscal Year 2024 Accelerating Cancer Screening awardees announced today:

Sign Up for Email Updates

Receive the latest updates from the Secretary, Blogs, and News Releases

Subscribe to RSS

Receive latest updates

Related News Releases

Biden-harris administration announces more than $68 million to improve access to hiv care for women, infants, children and youth, hhs, treasury, and interior departments and the executive office of the president aim to reduce administrative burden for tribal grant recipients, biden-harris administration invests over $200 million to help primary care doctors, nurses, and other health care providers improve care for older adults, related blog posts.

Upholding Research Integrity at HHS

Media inquiries.

For general media inquiries, please contact  [email protected] .

Disclaimer Policy: Links with this icon ( ) mean that you are leaving the HHS website.

• The Department of Health and Human Services (HHS) cannot guarantee the accuracy of a non-federal website.
• Linking to a non-federal website does not mean that HHS or its employees endorse the sponsors, information, or products presented on the website. HHS links outside of itself to provide you with further information.
• You will be bound by the destination website's privacy policy and/or terms of service when you follow the link.
• HHS is not responsible for Section 508 compliance (accessibility) on private websites.

For more information on HHS's web notification policies, see Website Disclaimers .

Progress in Cancer Research

Basic, molecular, epidemiologic, and clinical research are leading to improved cancer prevention, screening, and treatment. Decreasing cancer mortality death rates and increasing numbers of cancer survivors are important indicators of the progress we have made. As the leader of the National Cancer Program, NCI has played a major role in the progress that has been made by the cancer community. But work still needs to be done to reduce the burden of cancer for those who face a diagnosis.

Progress in research depends on the work of individual scientists and research institutions—universities and medical centers across the country, the NCI-designated cancer centers, the National Clinical Trials Network, the NCI Community Oncology Research Program—as well as collaborations between the private and public sector. In this section, we highlight the stories behind some notable milestones and present data about ongoing progress.

Annual Report to the Nation on the Status of Cancer

The Annual Report to the Nation on the Status of Cancer is an update of rates for new cases, deaths, and trends for the most common cancers in the United States.

Cancer Trends Progress Report

The Cancer Trends Progress Report summarizes the nation’s advances against cancer in relation to Healthy People targets set out by the Department of Health and Human Services.

Research Advances by Cancer Type

Find NCI’s collection of research advances for common cancers such as breast cancer, colorectal cancer, leukemia, lung cancer, and prostate cancer.

Stories of Discovery

Collection of stories that describe landmark developments in cancer prevention and treatment supported by NCI funding.

Milestones in Cancer Research and Discovery

During the past 250 years, we have witnessed many landmark discoveries in our efforts to make progress against cancer, an affliction known to humanity for thousands of years. This timeline shows a few key milestones in the history of cancer research.

• Share full article

Advertisement

Supported by

Study Puts a $43 Billion Yearly Price Tag on Cancer Screening

The estimate focused on five cancers for which there is medically recommended screening — breast, cervical, colorectal, lung and prostate — and found that colonoscopies accounted for most of the costs.

By Gina Kolata

The United States spent $43 billion annually on screening to prevent five cancers, according to one of the most comprehensive estimates of medically recommended cancer testing ever produced.

The analysis, published on Monday in The Annals of Internal Medicine and based on data for the year 2021, shows that cancer screening makes up a substantial proportion of what is spent every year on cancer in the United States, which most likely exceeds $250 billion. The researchers focused their estimate on breast, cervical, colorectal, lung and prostate cancers, and found that more than 88 percent of screening was paid for by private insurance and the rest mostly by government programs.

Dr. Michael Halpern, the lead author of the estimate and a medical officer in the federally funded National Cancer Institute’s health care delivery research program, said his team was surprised by the high cost, and noted that it was likely to be an underestimate because of the limits of the analysis.

For Karen E. Knudsen, the chief executive of the American Cancer Society, the value of screening for the cancers is clear. “We are talking about people’s lives,” she said. “Early detection allows a better chance of survival. Full stop. It’s the right thing to do for individuals.”

“We screen for cancer because it works,” Dr. Knudsen added. “The cost is small compared to the cost of being diagnosed with late-stage disease.”

Other researchers say the finding supports their contentions that screening is overused, adding that there is a weak link between early detection and cancer survival and that the money invested in cancer testing is not being well spent.

We are having trouble retrieving the article content.

Please enable JavaScript in your browser settings.

Thank you for your patience while we verify access. If you are in Reader mode please exit and  log into  your Times account, or  subscribe  for all of The Times.

Thank you for your patience while we verify access.

Already a subscriber?  Log in .

Want all of The Times?  Subscribe .