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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: Deciphering the underlying biology of drug resistance to improve patient response to targeted therapies.
Impact: Advances in cancer therapy have been a major contributor to the decline in breast cancer deaths over the last two and a half decades. Even with these advances, however, drug resistance – when tumors either do not respond at all or become resistant to anti-cancer drugs – remains a serious clinical challenge. Dr. Chandarlapaty 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 for breast cancer patients.
What’s next: In the coming year, Dr. Chandarlapaty will pursue laboratory studies focused on characterizing gene mutations that lead to treatment resistance following both anti-estrogen treatment and treatment with 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 options 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: To decipher the underlying biology of how breast cancer cells become resistance to therapy and devising strategies to prevent drug resistance.
Impact: Alterations in DNA are a common source of the abnormal cellular programs that convert a normal mammary cell into a breast cancer cell. These mutations not only cause cancer, but also prevent drugs from working properly. Thus, while targeted therapies aimed at these specific drivers of tumor growth have shown great success, resistance to these therapies 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 and his team are identifying the mutations that promote cancer growth and drug resistance and determining how they function. The results of their studies will inform the development of novel strategies to overcome resistance and improve outcomes for patients.
Current investigation: He and his team are focusing on one gene mutation that may contribute to resistance to hormonal treatment. They are also identifying mutations that cause resistance to a newly approved P13K inhibitor, alpelisib.
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 have 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. In other preliminary studies, they have found that the FOXA1 gene mutation, which occurs in 2-5 percent of breast cancers, may contribute to resistance to hormonal treatments.
What’s next: Dr. Chandarlapaty and his colleagues will continue to focus on the FOXA1 gene mutation. In addition, they will use data from a clinical trial study conducted at MSKCC to identify mutations that cause resistance to the P13K-inhibitor, alpelisib. Through these efforts, they hope to identify new approaches to overcome the effects of these mutations and prevent or delay drug resistance.
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.