MSK Research Highlights September 29, 2023

New research from Memorial Sloan Kettering Cancer Center (MSK) develops a method for analyzing cancer cells that survive treatment for acute myeloid leukemia; identifies a transcription factor that orchestrates natural killer cell response; and finds vepafestinib is a promising therapeutic for the treatment of RET-driven cancers.

New test analyzes cells that survive treatment in acute myeloid leukemia

Most people with acute myeloid leukemia (AML) eventually have the cancer return after treatment, due in large part to the phenomenon called measurable residual disease (MRD) — the small number of tumor cells that are able to survive treatment. The characterization of various MRD clones is important for predicting which patients are most likely to have the disease come back, making it useful for guiding decisions about therapy. Now a team from MSK has designed a new test to analyze these remaining cancer cells at the single-cell level.

Physician-scientist Ross Levine, MD, and pathologist Wenbin Xiao, MD, PhD, a member of Dr. Levine’s lab in the Human Oncology and Pathogenesis Program, led the development of the test, which combines flow cytometry with single-cell DNA analysis and immunophenotyping. The test not only enables the identification of relevant MRD clones with high sensitivity but it also allows researchers to learn more about how these cells are able to evolve and survive cancer therapy. Read more in Science Advances.

MSK-led team identifies transcription factor that orchestrates natural killer cell response

Natural killer (NK) cells are a type of immune cell that attack and kill infected cells and tumors. In a new study from the lab of the Sloan Kettering Institute’s Joseph Sun, PhD, and collaborators, researchers investigated the coordination of signals that are necessary for optimal NK cell responses during viral infections. Signals from antigens, co-stimulatory molecules, and pro-inflammatory cytokines are all required for the proper functioning of NK cells during viral infections in both mice and humans — and the team found that the transcription factor IRF4 plays a crucial role in integrating these signals and coordinating the response of NK cells. When IRF4 was absent, the functioning of NK cells was hampered. This was partially due to the inability of IRF4-deficient NK cells to take up necessary nutrients. Overall, the study, which was led by graduate student Endi Santosa, suggests IRF4 acts as a secondary metabolic checkpoint to orchestrate the adaptive response of NK cells during viral infections. The findings could help improve NK cell-based therapeutics. Read more in Nature Immunology.

Vepafestinib is a promising therapeutic for the treatment of RET-driven cancers

A next-generation RET inhibitor called vepafestinib holds promise against RET-driven cancers, a new study by an international research team led by MSK, Switzerland-based Helsinn Healthcare SA, and Japan-based Taiho Pharmaceutical finds. RET receptor tyrosine kinase is a protein that plays a role in various types of cancer, including lung, thyroid, colon, and pancreatic cancer. Small-molecule RET kinase inhibitors have become the standard therapy for advanced cancers driven by RET — but their effectiveness has been limited by acquired mutations and difficulty in reaching tumors that have spread to the brain. Now, a team of researchers co-led by Igor Odintsov, MD, Marc Ladanyi, MD, and Romel Somwar, PhD, of the Marc Ladanyi Lab in MSK’s Department of Pathology and Laboratory Medicine and Human Oncology and Pathogenesis Program, have found that vepafestinib has superior selectivity against RET than current drugs, good effectiveness against common resistance-causing mutations, and improved properties for penetrating the brain. The findings suggest that vepafestinib is a compelling candidate for use in patients with RET-driven cancers. Read more in Nature Cancer.