cancer research articles 2021

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Cancer Statistics, 2021

Affiliation.

• 1 Surveillance and Health Services Research, American Cancer Society, Atlanta, Georgia.
• PMID: 33433946
• DOI: 10.3322/caac.21654
• Erratum to "Cancer statistics, 2021". [No authors listed] [No authors listed] CA Cancer J Clin. 2021 Jul;71(4):359. doi: 10.3322/caac.21669. Epub 2021 Apr 19. CA Cancer J Clin. 2021. PMID: 34232515 No abstract available.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

Keywords: cancer cases; cancer statistics; death rates; incidence; mortality.

© 2021 American Cancer Society.

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New cancer treatment may reawaken the immune system

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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.

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12 cancer research breakthroughs of 2021

2021 has been a fantastic year for science with the rollout of the coronavirus vaccine happening at unprecedented speed thanks to the hard work of people around the world. And all through this turbulent time, cancer researchers have been hard at work too. Here are the 12 big cancer research breakthroughs made by our scientists in 2021.

The start of potential new cancer cures

Our scientists in Spain uncovered how a fat molecule found in palm oil, called palmitic acid, alters the cancer genome, and increases the likelihood cancer will spread. The researchers have started developing therapies that interrupt this process and say a clinical trial could start in the next couple of years.

Researchers in Italy discovered a new way to treat acute leukaemia by engineering immune cells taken from healthy donors and using them to target and destroy blood cancer cells. The team hope this could be the start for a new way to treat leukaemia in the future.

In Spain, researchers made a discovery that could help protect against diet-induced obesity and its related health issues. They found that by blocking a protein present in fatty tissue of obese mice could provide protection from weight gain caused by a high fat diet. Their findings could have major implications for obesity related diseases such as cancer.

Our scientists in London developed a new way to deliver drugs that can shut down cancer-promoting mutations in neuroblastoma. The findings show that the new delivery method, which uses tiny bubbles to deliver their cargo directly to the tumour cells, could form the basis for a new treatment for this common childhood cancer.

In Ireland, researchers supported by a collaboration between Worldwide Cancer Research and The Brain Tumour Charity discovered how a genetic mutation causes diffuse midline glioma – a childhood brain cancer also known as DIPG. Their discovery shows that it is possible to reverse the effects of the mutation to slow cancer growth.

Researchers in the Netherlands discovered a better understanding of how bowel cancer develops and identified a new way to prevent it. The research has now resulted in a clinical trial that will aim to repurpose a psychiatric drug as a new preventive cancer treatment in a group of people that – without intervention – are virtually 100% likely to develop bowel cancer in their lifetime.

Our scientists in France discovered how the tissue surrounding breast cancer tumours can prevent immune cells from reaching and destroying cancer cells. Their findings could lead to better ways to diagnose breast cancer and new ways to improve immunotherapy.

Researchers in Spain co-funded by AECC FC found a potential new way to treat highly aggressive pancreatic cancer. Their findings pave the way to design new treatment combinations that could kill cancer cells while also making them more susceptible to chemotherapy.

We found out that research we funded in 2005 helped to launch clinical trials testing a promising new treatment option for people with bowel cancer. The research revealed how a specific group of immune cells in the body can ‘mask’ the immune responses normally triggered to fight the cancer and have now sparked clinical trials testing a drug that can remove these cells, unmask the immune system, and open the tumour for attack. It’s hoped that this treatment could help prevent the disease from returning and improve survival rates for those with bowel cancer.

In Argentina, scientists made an exciting new discovery that could lead to the start of new clinical trials for prostate cancer. Their findings reveal a new treatment strategy that helps make immunotherapy work more effectively to kill off the most aggressive types of prostate cancer.

An international study shone a light on the impact the coronavirus pandemic had on the lives of people with liver cancer. Rates of liver cancer in the UK have increased by more than two and a half times since the early 1990s and continue to rise. Liver cancer now affects more than 6,000 people each year in the UK and only about 1 in 8 people survive for 5 years or longer after their diagnosis.

And finally, we were delighted to be able to commit to funding £4.5m on 23 new research projects that will start in 2022! These innovative new ideas from scientists all over the world are crucial for us to end cancer by starting new cancer cures of the future.

Incredible discoveries like this would not happen without research – and research cannot happen without the support of people like you. If you’re feeling inspired, why not help us make the breakthroughs of the future by donating and starting new cancer cures today?

Donate now & become a Curestarter

Be part of a united effort to stop lives being cut short by cancer.

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Cancer Research in 2021

Cancer research has been severely impacted by COVID-19. What does the future of cancer research look like in the new year after the pandemic?

Keeping Patients at the Center

Solange Peters

Lausanne University Hospital and European Society of Medical Oncology (ESMO)

With oncology being an area experiencing rapid growth, the topic of sustainability of healthcare systems is no longer avoidable. Oncology professionals will increasingly face situations where they will have to select treatments based on their allocated budgets. As physicians, researchers, caregivers, and politicians, one of our missions is to facilitate equal access to optimal cancer care for all patients.

From the research side, supporting solid science above marketing, allowing for the transition from all-comers treatment strategies to personalized approaches still represents an unmet need. The ongoing academic search for biomarkers that will allow us to optimize and rationalize cancer immunotherapy delivery represents an obvious example.

From the clinical side, the European Society for Medical Oncology (ESMO) developed a robust tool, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), to determine the benefit of systemic anticancer therapies in a rational and robust manner. ESMO-MCBS also serves as a screening tool to identify cancer treatments that have potential therapeutic value and warrant full evaluation for inclusion on the WHO Essential Medicines List. To complement it, ESMO is currently working on a geographically adapted value-based reimbursement model that aims to tackle issues related to the reimbursement of innovative medicines. As importantly and beyond, ESMO will create a new foundation in 2021 to start to work together following these aims, no matter where our patients are.

Optimism in Cancer Research

Peking University Health Science Center

The malignant cancers present a global threat to human health. Currently, there are still limited efficacious therapies to fight these diseases. It requires great additional efforts to develop more effective treatment strategies in order to save more lives and improve life quality. As the end of the COVID-19 pandemic becomes sooner and more certain, given the upcoming access to vaccines, I hope important cancer research will thrive in the year of 2021.

To explore the underlying mechanism(s) of tumorigenesis, multi-omics analyses including genomics, epigenomics, transcriptomics, proteomics, and metabolomics can be used to obtain multi-dimensional and dynamic insights. Additionally, multi-omics studies are critically important to identify molecular markers to diagnose cancer early, predict prognosis, and instruct individualized therapy. Moreover, big data approaches and AI technologies are particularly powerful for optimizing clinical trials. Furthermore, improving cancer immunotherapy is urgently needed. Better understanding of how the tumor microenvironment becomes suppressive and how tumor cells evade immune surveillance can provide insights to develop new therapeutics. Combinations of different types of immunotherapy, targeted therapy, and chemo and radiation therapy might help overcome resistance. Finally, population and epidemiological studies can help realize precision prevention. The high-risk groups can be identified using effective molecular markers, which will promote the utilization of effective intervention approaches and reduce cancer occurrence.

A New Normal

Sherene Loi

Peter MacCallum Cancer Centre

As we are nearing the end of this incredible year, it feels that 2020 never actually came to pass; yet massive changes have occurred to facilitate clinical practice during the COVID-19 pandemic. For example, clinical trials became more accessible, as border closures meant that many patients could not travel to trial sites. Telehealth became the norm, and satellite sites could deliver study medication. In Australia, our large and sparsely populated country, these changes will be of considerable benefit to all cancer patients and augment clinical trial participation.

Laboratory research, however, did suffer, as the prolonged lockdown restrictions on personnel and animal work meant that most of the basic research at Peter Mac came to a grinding halt. When much of our research is focused on the immune microenvironment, work with models that have competent immune systems is vital.

With Australia’s geographic location, researchers will also miss the interactions during international conferences, as we are now unable to travel until a vaccine is widely implemented. Who knows what collaborative opportunities may have been missed due to these forced border constraints. Critical issues in immunology-based cancer research remain similar to those in 2019: identifying new immune targets, devising biomarkers that can predict those patients who will respond to checkpoint inhibition and those who will need more, bispecific agents that engage the patient’s immune system and induce epitope spreading, and next-generation CAR-Ts and antibody conjugates, for example. However, like a branch in Darwin’s evolutionary tree, Australia could be moving on a different tangent until travel is widely possible again. One refreshing local consequence of COVID-19 has been that researchers from diverse disciplines have come together to address the pandemic. A notable example of this is that cancer researchers from the Peter Mac, who were using CRISPR-Cas13b to target oncogenic mRNA transcripts for degradation, collaborated with infectious disease researchers from the Doherty Institute, together adapting the technology to degrade SARS-CoV-2 genomic RNAs. The approach suppressed viral replication in vitro by up to 90% as well as mutation-driven viral evolution. The strategy may prove effective for those infected with SARS-CoV-2 but may also potentially be applied to combat other viruses, including those that cause cancer.

A Turning Point

Tobiloba Oni

Cold Spring Harbor Laboratory

In January 2020, most people were unbothered, blithely planning for another regular year. However, the COVID-19 pandemic upended those plans and radically changed our daily lives. The science world dramatically changed, too. Experiments ground to a halt for most scientists, scientific exchange became virtual, and we had to adapt to a new reality. In May 2020, most of us were still adjusting to the new normal until the killing of George Floyd ruptured that normalcy and laid bare the systemic racism that perpetuates bias and inequalities in science.

One year into the pandemic and only a few months after the harrowing events in Minneapolis, we now stand at a turning point. We have a real chance to not only address the long-standing disparities in our scientific communities but also to reimagine scientific exchange. The constraints imposed by the pandemic have made scientific conferences and workshops more accessible; collaborations have soared, and discoveries are being rapidly disseminated. Similarly, the awakening to the racial disparities in science has prompted concerted efforts from individuals, scientific organizations, and funding agencies to devise action plans to increase and support diversity in science. If these efforts are sustained, I envision a more diverse scientific workforce with an increased ability to solve the most challenging scientific problems. As the new year begins and the world awaits a return to normalcy, I hope science does not return to the old normal.

Prostate Cancer Research Results and Study Updates

See Advances in Prostate Cancer Research for an overview of recent findings and progress, plus ongoing projects supported by NCI.

Under a new FDA approval, enzalutamide (Xtandi) can now be used alone, or in combination with leuprolide, to treat people with nonmetastatic prostate cancer that is at high risk of returning after surgery or radiation.

FDA approved enzalutamide (Xtandi) combined with talazoparib (Talzenna) for metastatic castration-resistant prostate cancer with alterations in any of 12 DNA repair genes. The drug combination, which blocks both DNA repair activities and hormones that fuel cancer growth, was more effective than the standard treatment in a large clinical trial.

The Decipher genomic test found high-risk prostate cancer even when conventional tests said the tumors were lower risk. This discrepancy appeared to happen more frequently for African-American men.

Men diagnosed with low-risk prostate cancer are increasingly opting against immediate treatment and choosing active surveillance instead, a new study finds. In fact, rates of active surveillance more than doubled between 2014 and 2021.

Adding darolutamide (Nubeqa) to ADT and docetaxel (Taxotere) can improve how long men with hormone-sensitive metastatic prostate cancer live without causing more side effects, results from the ARASENS trial show.

Many with prostate cancer can safely receive shorter, higher-dose radiation therapy after surgery, a new study has found. The approach, called HYPORT, didn’t harm patients’ quality of life compared with the standard radiation approach, trial finds.

A drug called Lu177-PSMA-617 may be a new option for treating advanced prostate cancer. In a large clinical trial, adding the drug—a type of radiopharmaceutical—to standard treatments improved how long participants lived.

For some men with prostate cancer, a genetic biomarker test called Decipher may help predict if their cancer will spread elsewhere in the body. The test could help determine whether hormone therapy, which can cause distressing side effects, is needed.

FDA’s recent approval of relugolix (Orgovyx) is expected to affect the treatment of men with advanced prostate cancer. A large clinical trial showed that relugolix was more effective at reducing testosterone levels than another common treatment.

FDA has approved olaparib (Lynparza) and rucaparib (Rubraca) to treat some men with metastatic prostate cancer. The PARP inhibitors are approved for men whose cancers have stopped responding to hormone treatment and have specific genetic alterations.

For some men with prostate cancer at high risk of spreading, a large clinical trial shows an imaging method called PSMA PET-CT is more likely to detect metastatic tumors than the standard imaging approach used in many countries.

Testing for prostate cancer with a combined biopsy method led to more accurate diagnosis and prediction of the course of the disease in an NCI study. The method is poised to reduce the risk of prostate cancer overtreatment and undertreatment.

In the Veterans Affairs health care system—where all patients have equal access to care—African American men did not appear to have more-aggressive prostate cancer when diagnosed or a higher death rate from the disease than non-Hispanic white men.

In two large clinical trials, the drugs enzalutamide (Xtandi) and apalutamide (Erleada), respectively, combined with the androgen deprivation therapy, improved the survival of men with metastatic prostate cancer that still responds to hormone-suppressing therapies.

The Prostate Cancer Prevention Trial showed that finasteride can reduce the risk of prostate cancer, but might increase the risk of aggressive disease. NCI’s Howard Parnes talks about subsequent findings and what they mean for men aged 55 and older.

The investigational drug darolutamide can help delay the spread of prostate cancer in some men with the disease, a recent clinical trial shows. In addition, the drug caused fewer side effects than similar prostate cancer drugs.

For African American men, the risk of dying from low-grade prostate cancer is double that of men of other races, a new study has found. But, despite the increase, the risk is still small.

Researchers have found that men with advanced prostate cancer may be more likely than previously thought to develop a more aggressive form of the disease. The subtype, called t-SCNC, was linked with shorter survival than other subtypes.

RESPOND is the largest coordinated study on biological and non-biological factors associated with aggressive prostate cancer in African-American men. The study is an effort to learn why these men disproportionally experience aggressive disease.

In a small clinical trial, researchers compared the efficacy of a much lower dose of the cancer drug abiraterone (Zytiga) taken with a low-fat breakfast with a full dose taken on an empty stomach, as directed on the drug’s label.

In the trial that led to the approval, apalutamide (Erleada) delayed cancer metastasis for men with prostate cancer that is resistant to androgen deprivation therapy.

A new study in mice has revealed a molecular link between a high-fat diet and the growth and spread of prostate cancer. The findings, the study leaders believe, raise the possibility that changes in diet could potentially improve treatment outcomes in some men.

The Food and Drug Administration (FDA) has expanded the approval of abiraterone (Zytiga®) for men with prostate cancer. The agency approved abiraterone, in combination with the steroid prednisone, for men with metastatic prostate cancer that is responsive to hormone-blocking treatments (also known as castration-sensitive) and is at high risk of progressing.

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U.S. cancer incidence trends lower than expected in 2021

by Elana Gotkine

U.S. cancer incidence trends improved in 2021, but continued to be lower than expected, according to a study published online Sept. 6 in JAMA Network Open .

Todd Burus, from the University of Kentucky in Lexington, and colleagues conducted a cross-sectional, population-based study of cancer incidence trends using the Surveillance, Epidemiology, and End Results 22 (SEER-22) Registries Database to examine observed versus expected cancer rate trends for January 2020 to December 2021.

In 2020 and 2021, the SEER-22 registries reported 1,578,697 cancer cases (50.6 percent among males and 57.6 percent among persons aged 65 years or older). The researchers found that all-sites cancer incidence rates were 9.4, 2.7, and 6.0 percent lower than expected in 2020, 2021, and in both years combined, respectively, resulting in 149,577 potentially undiagnosed cancer cases. Of the four screening-detected cancers, in 2021, there was a significant recovery for female breast cancer only (expected rates exceeded by 2.5 percent), while significant reductions persisted for lung cancer and cervical cancer (9.1 and 4.5 percent lower than expected, respectively), especially for early stage at diagnosis. Among female individuals, persons aged younger than 65 years, and persons of non-Hispanic Asian and Pacific Islander race and ethnicity, rates of all-sites cancer incidence returned to prepandemic trends.

"This study suggests that cancer cases in the U.S. continued to be underdiagnosed during the second year of the COVID-19 pandemic," the authors write. "Particular attention should be directed at strategies to immediately increase cancer screenings to make up lost ground and prevent a future surplus of late-stage diagnoses."

One author disclosed ties to the pharmaceutical industry .

Copyright © 2024 HealthDay . All rights reserved.

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Focus  21 December 2021

2021 in Review

Nature Cancer’s 2021 in Review Focus comprises a series of specially commissioned articles in which leading experts in the cancer field offer their unique perspectives on the most exciting advances and the biggest challenges of the past year. These articles are accompanied by an editorial selection of highlights from the cancer literature and a collection of some of the most popular primary research articles published in Nature Cancer over the last 12 months.

Editorial & News

It’s a wrap for 2021.

In our Focus on 2021 in Review , the Nature Cancer team and leading experts look back at the biggest developments for the cancer field over the past 12 months.

Cancer drug approvals and setbacks in 2021

From a first-in-class KRAS approval to the latest agonist antibody failures, 2021 was another busy year for cancer drug developers.

• Asher Mullard

Cancer’s new normal

Despite widespread vaccination, patients with cancer still face a slew of pandemic-related challenges.

• Elie Dolgin

Cancer research that matters

Elisabete Weiderpass is an expert in cancer epidemiology and cancer prevention. She has been the Director of the International Agency for Research on Cancer, the specialized cancer agency of the World Health Organization, since January 2019. She spoke with Nature Cancer about 2021 and the years ahead.

• Alexia-Ileana Zaromytidou

Reflecting on the golden age of cancer research

50 years after the National Cancer Act was signed into law, Nature Cancer spoke with the National Cancer Institute Director Dr Ned Sharpless about the progress in cancer research and care, the complications of the pandemic and what to expect in the future.

Comment & Analysis

LAG-3 and PD-1 blockade raises the bar for melanoma

Combination of approved immune checkpoint inhibitors has shown remarkable efficacy in the treatment of melanoma, but at the cost of high toxicity. After years of intensive research, inhibitors of the immune checkpoint molecule LAG-3 are now demonstrating promising results and favorable toxicity profiles in clinical trials in combination with inhibition of the checkpoint molecule PD-1.

• Caroline Robert

KRAS inhibitors, approved

The rapid progression of KRAS(G12C) inhibitors from preclinical characterization to the clinic has radically changed the perception of the KRAS oncogene as an undruggable target. Here we discuss ongoing and future possibilities for developing therapies using these inhibitors in clinical settings.

• Rafael Rosell
• Andrés Aguilar
• Imane Chaib

COVID-19 and cancer care in India

The COVID-19 pandemic has impacted cancer care globally, the consequences of which are still not well understood. Through the lens of the impact in India, we emphasize the importance of continuing cancer care even during extenuating public health circumstances, and of strengthening health systems as a global priority.

• C. S. Pramesh
• Girish Chinnaswamy
• Rajendra Badwe

The emergence of cancer genomics in diagnosis and precision medicine

Rapid progress in the molecular characterization of cancer genomes has been enabled by technology and computational analysis, and large databases now exist. Novel cancer therapeutics have resulted that more precisely target the vulnerabilities revealed by genomic analysis. Emergent efforts that link the two, using machine learning approaches and circulating DNA from cancer cells, are furthering cancer diagnosis and precision medicine.

• Elaine R. Mardis

Completing the cancer jigsaw puzzle with single-cell multiomics

Recent advances in single-cell multiomics have provided holistic views of the multifaceted state of a cell and its interaction with the environment. The rapid development of these technologies has offered a unique opportunity to analyse the molecular and cellular heterogeneity in cancer, and could lead to better cancer diagnosis, treatment and prognosis.

• Sarah A. Teichmann

Stargazing through the lens of AI in clinical oncology

Cancer multi-omics data has greatly expanded over recent decades, surpassing the human ability to extract meaningful information. The successful implementation of artificial intelligence systems into clinical pipelines to interpret complex datasets, and improve the outcomes of patients with cancer, demands strong validation using real-world evidence while also being mindful of ethical and social aspects.

• Constance D. Lehman
• Shandong Wu

Harnessing the microbiome to restore immunotherapy response

Despite the profound clinical success of immune-checkpoint inhibitors, their effectiveness is limited by intrinsic and acquired resistance. Bullman, Zitvogel and colleagues provide their views on two clinical trials modulating the microbiome of immunotherapy-resistant patients with melanoma via transplantation of fecal microbiota from patients who responded to immunotherapy.

• Susan Bullman
• Alexander Eggermont
• Laurence Zitvogel

Challenges and opportunities in 2021

Twelve early-career investigators share their thoughts on the challenges faced by their teams and communities during the past year, and look ahead to new opportunities for 2022.

• Leila Akkari
• Stacey D. Finley
• Meng Michelle Xu

Research Highlights

Gemys homing in on metastasis, fusion proteins drive cancer through phase separation.

• Ioanna Pavlaki

Front-line immunotherapy combinations for gastric cancer

• Miguel Foronda

Fitting whole-genome sequencing analysis for metastasis

• Julia Simundza

Cancer cells remember a fatty diet

Outcompeting neighbors for intestinal cancer initiation, rna splicing meets anti-tumor immunity, neoantigens take center stage, probing clonal dynamics with single-cell genomics, nature cancer research articles.

Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities

Garofano et al. use single-cell RNA-sequencing data to classify glioblastomas along a metabolic axis of mitochondrial and glycolytic/plurimetabolic states and a neurodevelopmental axis of proliferative/progenitor and neuronal states.

• Luciano Garofano
• Simona Migliozzi
• Antonio Iavarone

Few-shot learning creates predictive models of drug response that translate from high-throughput screens to individual patients

Ma et al. apply few-shot learning to train a neural network model on cell-line drug-response data, and they subsequently transfer it to distinct biological contexts including different tissues and patient-derived tumor cells and xenografts.

• Samson H. Fong
• Trey Ideker

Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors

Walsh and colleagues use prospective sequencing in a large cohort of pediatric patients with solid tumors to detect mutations in cancer predisposition genes and guide downstream clinical care.

• Elise M. Fiala
• Gowtham Jayakumaran
• Michael F. Walsh

Fatty acid synthesis is required for breast cancer brain metastasis

Ferraro et al. report that fatty acid synthesis is needed for brain cancer metastasis and show that blocking this process by inhibiting fatty acid synthase reduces the metastatic growth of breast cancer cells in the brain.

• Gino B. Ferraro
• Matthew G. Vander Heiden

Neutrophil oxidative stress mediates obesity-associated vascular dysfunction and metastatic transmigration

Quail and colleagues demonstrate that neutrophil-derived ROS and extracellular traps (NETs) mediate breast cancer metastasis to the lungs by altering endothelial junctional adhesions, thus favoring vascular permeability and transendothelial migration of cancer cells.

• Sheri A. C. McDowell
• Robin B. E. Luo
• Daniela F. Quail

A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors

D’Andrea and colleagues identify the antibiotic novobiocin as a specific POLQ inhibitor with preclinical activity in homologous-recombination-deficient breast and ovarian tumors in vivo, including these with acquired PARP inhibitor resistance.

• Camille Gelot
• Alan D. D’Andrea

Acquired resistance to anti-MAPK targeted therapy confers an immune-evasive tumor microenvironment and cross-resistance to immunotherapy in melanoma

Obenauf and colleagues report that acquired resistance to BRAF and MEK inhibitors in melanoma confers cross-resistance to immune checkpoint blockade by fostering a cancer cell–instructed, immune-evasive tumor microenvironment.

• Anais Elewaut
• Anna C. Obenauf

Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression

Italiano and colleagues demonstrate the utility of mature tertiary lymphoid structures to predict response to immunotherapy, with pathologic analysis in three independent patient cohorts spanning multiple tumor types.

• Lucile Vanhersecke
• Maxime Brunet
• Antoine Italiano

Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced antitumor immunity

Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.

• Qingfeng Zhu
• Mark Yarchoan

Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia

Pappalardi and colleagues identify a potent noncovalent DNMT1-selective inhibitor with improved tolerability and efficacy in preclinical AML models compared with clinically validated covalent pan-DNMT inhibitors.

• Melissa B. Pappalardi
• Kathryn Keenan
• Michael T. McCabe

Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms

Lehtiö and colleagues perform proteogenomic analysis of non-small cell lung cancer and identify molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets and validate their classification method in separate clinical cohorts.

• Janne Lehtiö
• Taner Arslan
• Lukas M. Orre

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

• Annika Fendler
• Scott T. C. Shepherd
• The CAPTURE Consortium

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