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Sarat Chandarlapaty, MD, PhD
Associate Attending Physician
Laboratory Head, Human Oncology and Pathogenesis Program
Memorial Sloan Kettering Cancer Center
New York, New York
Member, BCRF Scientific Advisory Board
Goal: To decipher the underlying biology of how breast cancer cells become resistance to therapy and devising strategies to prevent drug resistance.
Impact: Advances in cancer therapy have been a major contributor to the decline in breast cancer deaths over the last two and half decades. Even with these, advances, drug resistance–when tumors either don’t respond at all or become resistant to anti-cancer drugs–remains a serious clinical challenge. Dr. Chandarlapaty’s research is focused on understanding how cancer cells evade the drugs designed to kill them in order to develop strategies to prevent or overcome drug resistance and improve outcomes in breast cancer patients.
What’s next: In the coming year, they will pursue laboratory studies that will focus on gene mutations that lead to resistance to anti-estrogen treatments and a targeted drug that blocks the PI3K tumor promoting pathway.
Breast cancers become incurable and ultimately lethal when they spread to other tissues in the body (metastasis). At this point, they are often resistant to a variety of drugs, exacerbating treatment for metastatic breast cancer. The goals of Dr. Chandarlapaty’s work are to identify mutations that promote cancer growth and drug resistance, determine how they function, and then develop strategies to overcome them to improve patient outcomes.
Full Research Summary
Research area: Solving the mysteries of drug resistance and improving response to targeted therapies.
Impact: While targeted therapies aimed at specific drivers of tumor growth have shown great success, resistance to these agents is common, resulting in tumor growth and spread. Breast cancers become incurable and ultimately lethal when they spread to other tissues – a process known as metastasis. Dr. Chandarlapaty is investigating gene mutations that prevent drugs from working properly with the goal of identifying new approaches to preventing or delaying drug resistance.
Current investigation: He and his team have been studying how breast cancers evade the systemic therapies that are currently utilized against them. They employ sophisticated laboratory models to study the biologic mechanisms at play to develop novel therapeutic strategies that can potentially overcome resistance and improve clinical outcomes.
What he’s learned so far: Dr. Chandarlapaty has determined how a complex set of changes in the number of chromosomes alters breast cancer biology for a subset of cancers. He and his team has also investigated the role of an aberrant signaling pathway in a subset of HER2-positive breast cancers. These findings have led to new insights into how these cancers elude anti-ER and anti-HER2 therapy.
What’s next: Dr. Chandarlapaty and his colleagues will focus on a gene mutation, FOXA1, that occurs in about 2-5 percent of breast cancer. Their early findings suggest FOXA1 may contribute to resistance to different hormonal treatments. team is currently studying a gene called FOXA1 that when mutated can lead to resistance of endocrine (anti-estrogen) therapies. In addition, they are developing strategies to improve response to an approved targeted therapy called alpelisib.
Sarat Chandarlapaty, MD, PhD, is an Associate Attending medical oncologist and a Laboratory Head in the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. He earned his medical degree at the Wake Forest School of Medicine and his PhD at the University of North Carolina. Dr. Chandarlapaty completed his residency at New York Presbyterian Hospital, and his fellowship at Memorial Sloan Kettering Cancer Center. A major focus of his work has been to characterize the significance of alterations present in metastatic tumors that have progressed following targeted therapies such as antiestrogens or CDK4/6 inhibitors, as well as to develop models of resistant cancer for testing newer therapeutic strategies.