Year in Review: Five Important Clinical Advances in Cancer in 2020

Memorial Sloan Kettering neuro-oncologist Adrienne Boire

Neuro-oncologist Adrienne Boire pictured in 2018. Her discovery about leptomeningeal metastasis, a devastating cancer complication, was among the top clinical advances made at MSK in 2020.

In 2020, Memorial Sloan Kettering clinical researchers continued to make major discoveries that will improve the treatment of cancer and guide the development of new therapies. Many of these studies were made possible by philanthropic donations, which allow researchers to pursue innovative ideas and take the risks necessary for breakthrough discoveries.

1. Precision Medicine for Lung and Thyroid Cancer

In May, the US Food and Drug Administration approved a drug called selpercatinib (Retevmo™) for lung and thyroid cancers that have a specific kind of genetic alteration called RET gene mutations or fusions. RET fusions occur when part of the gene gets rearranged and attaches itself to another gene. That creates what is called an oncogene, a kind of zombie gene that takes over normal behavior and drives cells to grow out of control — leading to cancer.

The FDA approval came after encouraging results from an international clinical trial testing the drug on cancers with RET fusions. The trial was led by MSK medical oncologist Alexander Drilon, Chief of the Early Drug Development Service, which conducts phase I trials of promising new targeted therapies for solid tumors in both adult and pediatric patients.

In September, a study was published in the New England Journal of Medicine that looked further at the outcomes of people treated with selpercatinib. It found that among people with lung cancer who had previously received other treatments, 64 percent had their tumors shrink substantially. After a year of taking the drug, nearly two-thirds of those patients were still responding well. For those who had never received any treatment, the response rate was even higher at 85%.

“This data – and the recent approval – confirm that RET-driven cancers are specifically targetable, marking another important step in the field of precision medicine,” Dr. Drilon explains.

Philanthropic support for the Early Drug Development Service and Dr. Drilon’s work has been provided by entrepreneur and philanthropist Michael Repole through his private foundation, Nonna’s Garden, since 2018.

2. Targeting an “Undruggable” Protein in Lung and Colorectal Cancer

The cancer gene KRAS is known to be responsible for many of the most common cancers. This includes about one-quarter of lung cancers and between one-third and one-half of colon and rectal cancers. Until recently, however, the KRAS protein was considered an “undruggable” target.

In September, in the New England Journal of Medicine (NEJM), investigators reported results from CodeBreak 100, the first-ever clinical study of a drug that directly targets the KRAS protein. In this international phase 1 trial, researchers found that a drug called sotorasib (AMG 510) slowed or stopped cancer growth in many people with advanced cancer containing a version of the mutant KRAS protein called KRAS-G12C.

“Sotorasib is not a cure, but this study is the first to crack KRAS in a clinically meaningful way,” says MSK medical oncologist Bob Li, a senior investigator and corresponding author of the study.

The researchers found a small pocket in KRAS-G12C that opens and closes and designed a drug to fit into it when it opens. “When one of these drugs goes in the protein’s pocket, it traps KRAS-G12C in its ‘off’ state,” says MSK physician-scientist Piro Lito, a senior author on the NEJM paper. “The protein can’t wake up, and the tumor cells cannot grow.”

The investigators say much more research is needed to determine how to best use this drug, but this trial is a significant first step.

Philanthropic support for this research was provided by the Pew Charitable Trusts and the Damon Runyon Cancer Research Foundation.

3. A Novel Treatment Strategy  for Leptomeningeal Metastasis

Cancer that has spread to the fluid and tissues of the brain and spinal cord, called leptomeningeal metastasis, has become a more common complication of cancer. This is mainly because people are living longer after treatment of their primary tumors. It is a difficult cancer to treat because brain and spinal cord fluid are largely sealed off from the rest of the body by a tight barrier. In addition, doctors have been puzzled by how the cancer cells grow there — there is a dearth of iron in the area that cancer cells usually rely on to fuel their growth.

But a team of MSK researchers led by neuro-oncologist Adrienne Boire and computational biologist Dana Pe’er may have found the cancer cells’ secret power: They reprogram themselves to gobble up all the nearby iron. By hogging this nutrient, the cancer cells ensure they stay alive and grow while other cells — notably immune cells that have entered the same space — are left short.

“It’s really unique biology that allows cancer cells to win the competition,” Dr. Boire says. The researchers published their discovery on July 16 in Science. They say the finding also points to a possible strategy for treatment – cutting off the cancer cells’ access to iron in the surrounding area.

Philanthropic support for Dr. Boire’s research was provided by Pew Charitable Trusts, the Damon Runyon Cancer Research Foundation, the Pershing Square Sohn Cancer Research Alliance, and the Baker Family Foundation.

4. New Hope for Some People with Advanced Colorectal Cancer

In April, the FDA approved a combination therapy using two targeted drugs for the treatment of aggressive colorectal cancer. The drugs, encorafenib (Braftovi®) and cetuximab (Erbitux®), were shown to be effective when given in combination to people with tumors that have a mutation called BRAF V600E. About 8% to 10% of all people with colorectal cancer have a BRAF V600E mutation in their tumor.

MSK had a leading role in the research that developed this combination therapy.

“It’s a big improvement because this cancer type is very aggressive after it spreads [metastasis] and other treatments have failed,” says medical oncologist Rona Yaeger. “The trial showed that this combination therapy not only helps people live longer but can delay the development of these symptoms and improve their quality of life.”

Philanthropic support for the research leading to the development of this therapy was provided by the Conquer Cancer Foundation and The Society of MSK.

5. A Prostate Cancer Treatment that Targets Tumor “Aiders and Abettors”

Cancer doesn’t exist on its own within the body. It thrives within what is called the tumor microenvironment — the ecosystem of tissues, blood vessels, immune cells, and noncancerous components surrounding a tumor. A team of MSK doctors and researchers reported they found a protein within the microenvironment of certain prostate cancers that empowers the tumors to resist therapy.

Now that they’ve identified the protein, called NRG1, researchers think they may be able to block it and prevent therapy resistance.

“Until now, looking at the microenvironment as a cause of resistance to treatment hasn’t really been on our radar,” says physician-scientist Charles Sawyers, Chair of MSK’s Human Oncology and Pathogenesis Program and the paper’s senior author.

“This new research shows that resistance to treatment isn’t coming only from the tumor itself — it may also be caused by some aspect of the microenvironment,” says surgeon Brett Carver, a member of Dr. Sawyers’ lab who co-authored the paper.

Philanthropic support for this work was provided by the Vallee Foundation, the Prostate Cancer Foundation, the Dutch Cancer Foundation, the Welch Foundation, the WorldQuant Foundation, the Pershing Square Sohn Cancer Research Alliance, a University of Texas Southwestern (UTSW) Deborah and W.A. Tex Moncrief, Jr., scholarship, and a UTSW Harold C. Simmons Cancer Center Pilot Award.