image: An MSK researcher works in the lab.
Credit: Memorial Sloan Kettering Cancer Center
New research from Memorial Sloan Kettering Cancer Center (MSK) identifies a rare cell population responsible for AML persistence and resistance to therapy; sheds new light on early brain development; and investigates how other health conditions can increase cancer risk in midlife. MSK clinical trials also supported the recent approval of the targeted drug larotrectinib by the FDA.
MSK researchers identify rare cell population responsible for AML persistence and resistance to therapy
Many human cancers originate and grow from quiescent stem cells. Because these cells are rare, they tend to be difficult to isolate and continue to remain poorly understood. MSK researchers have now identified a rare, quiescent population of stem cells responsible for disease persistence and therapy resistance in acute myeloid leukemia (AML), a common blood cancer that affects children and adults. These cells hide from standard markers used to identify them, showing why traditional diagnostic and therapeutic approaches fail to target leukemia stem cells effectively.
Further, the team — led by senior study author Alex Kentsis, MD, PhD, Director of MSK’s Tow Center for Developmental Oncology, and first author Sumiko Takao, MD, PhD, now an assistant professor at Kanazawa University — identified several key factors, including the transcription factor JUN, as regulators of this quiescence. Their findings show JUN is required for maintaining quiescence and is associated with therapy resistance across diverse patient leukemias, thus making JUN and other quiescence regulators attractive targets for future therapies. This also includes MYB, for which new drugs are now being developed for clinical trials for patients.
“By addressing a fundamental challenge in leukemia — therapy resistance and relapse driven by quiescent leukemia stem cells — this approach has the potential to improve treatment strategies that are so desperately needed for survival and quality of life for leukemia patients,” Dr. Kentsis says. Read more in Nature Communications.
MSK researchers shed new light on early brain development
A team of MSK researchers is shedding new light on gene expression patterns during brain development in mammals using single-cell RNA sequencing — a technique to analyze gene expression at the level of individual cells. In a new study, they investigated how the cranial neural plate transforms from a flat sheet into a closed tube, serving as a structural framework for brain development.
The team created a map of gene expression at six consecutive stages of this process in mouse embryos. Not only did their map match the expression of known genes, they also were able to predict the expression of hundreds of unknown genes — which will help scientists understand the earliest stages of brain development and the processes that guide its spatial organization.
The group — led by first author Eric Brooks, PhD, a former research fellow at MSK now an assistant professor at North Carolina State University, and senior author Jennifer Zallen PhD, a developmental biologist at MSK’s Sloan Kettering Institute and a Howard Hughes Medical Institute investigator — additionally found that a key developmental pathway, Sonic hedgehog signaling, plays a critical role in the process. The study was a collaboration with the lab of MSK computational biologist Dana Pe’er, PhD.
Reviewers said the work “provides a fundamental demonstration of how different cell fates are organized in specific spatial patterns along the anterior-posterior and medial-lateral axes within the developing neural tissue,” noting the discovery was “compelling” because it “features methods, data, and analyses more rigorous than the current state-of-the-art.” Read more in eLife.
Other health conditions increase cancer risk in midlife
A variety of health problems tend to arise in midlife, but their relationship to cancer is poorly understood. Now, in an analysis of nearly 130,000 adults 55 to 74 with no history of cancer, researchers from MSK and their collaborators found those with respiratory and cardiovascular conditions were at significantly higher risk for developing cancer.
In their secondary analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial, which was conducted at 10 centers across the UnitedStates between 1993 and 2001, the team found the strongest cancer-specific association between people with a history of liver conditions and risk of liver cancer. They also found that some metabolic conditions (type 2 diabetes and obesity) were significantly associated with higher risk of nine cancer types — but lower risk for four other types.
The study could inform how doctors may help higher-risk patients with a variety of other health conditions by recommending they take preventive measures or undergo more frequent cancer screenings, says study first author Jessica Lavery, MS, a senior research biostatistician at MSK. Read more in JAMA Network Open.
Targeted drug larotrectinib receives full approval from the FDA
The U.S. Food and Drug Administration (FDA) granted full approval to the targeted therapy larotrectinib (Vitrakvi®) on April 10, 2025. The drug previously had received accelerated approval from the FDA, in November 2018. Larotrectinib is used to treat patients of any age with tumors anywhere in the body that are caused by mutations in the gene NTRK (EN-track).
The original approval of larotrectinib was a landmark. It was the first drug ever to be developed and approved based solely on its molecular activity, regardless of where in the body a tumor originated. The trials that resulted in that drug’s approval were led by MSK’s Early Drug Development Service, including its current chief, thoracic medical oncologist and early drug development specialist Alexander Drilon, MD.
“This full approval reinforces how well this drug works for children and adults who have cancers with an NTRK gene fusion,” Dr. Drilon says. “It provides a foundation for other agencies around the world to consider approving this drug, so the treatment will be available more patients.”