The Next Big Thing in Cancer Research

Patricia McKnight

April 28, 2023

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In the latest issue of Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years. 

More Sex-Specific Research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, Australia, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Loi's recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

"It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting," Loi said. 

The Global Cancer Community

C.S. Pramesh, MS, FRCS, director of the Tata Memorial Hospital in Mumbai, India, believes that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

"With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries," Pramesh said. "Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world."

Medscape contributor Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed "cancer groundshot."

Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research — goals that are critical but often not prioritized by high-income countries or industry, he said.

"Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good," Pramesh said.

Prioritizing Combination Therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, from The Netherlands Cancer Institute.

"Resistance to therapy remains a major obstacle in the treatment of cancer," Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with "nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic."

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

"I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets," he said. "Over time, this would also contribute to affordable healthcare through use of more generic drugs."

Cancer Drugs and the Heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Moslehi discovered that "many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship."

But, Moslehi explained, "we are entering [uncharted] waters."

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

"Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation," Moslehi explained.

Inside Rare Cancers

William Sellers, MD, director of the Broad Institute of MIT's Cancer Program, thinks rare cancers should be the next focus.

After all, "rare cancers are only rare in isolation," Sellers said, noting that these cancers make up 20% to 24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

"New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases," he said. 

Researchers have reported numerous relationships with pharmaceutical companies, as listed in the original article. 

Cell. Published online April 13, 2023. Full text

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