1). Resistance to targeting oncogenic effectors: CDK4/6i resistance
2). Resistance to targeting the mutant oncoprotein pathway: HER2/PI3K resistance.
3). Resistance to targeting the lineage: hormone receptors.
4). Resistance to targeting the surface targets: Antibody Drug Conjugates (ADCs)
5). Biomarkers and reagents to detect and suppress cancer evolution
The Chandarlapaty lab studies the molecular basis for resistance to targeted therapy in breast cancer with the goal of identifying treatment approaches that can overcome resistance and facilitate cures.
The goal of my research program is to understand the detailed mechanisms by which a cancer cell can develop resistance to therapies targeting its oncogenic driver; and to exploit those findings to elucidate the biology of cancer and identify more effective treatments for cancer patients. The focus of this work has been on signaling networks emanating from the hormone receptor, ER, and the receptor tyrosine kinase, HER2. These two signals play a dominant role in cancers of the breast, with roughly 85% of all tumors driven by one or both of these receptors. Whereas drugs targeting these signals have major benefits in patients, resistance to therapy is frequently encountered. Our studies have centered on (1) understanding how cancers evolve to resist therapies against ER, CDK4/6, HER2, and PI3K and (2) development of mechanism-based drugs or treatment strategies that can prevent or overcome these modes of resistance.
Biography
Sarat Chandarlapaty is a Physician-Scientist at MSKCC in New York. He graduated with a B.S. in Chemistry from the College of William and Mary, a PhD in Biochemistry from the University of North Carolina, and an M.D. from Wake Forest University. During his postdoctoral fellowship in the laboratory of Dr. Neal Rosen, Sarat studied regulation of PI3K/AKT signaling, leading to the understanding that cancer cells have activated feedback regulation of oncogenic networks that ultimately promote adaptive drug resistance. In 2012, Sarat joined the faculty at MSKCC and has focused on understanding the basis for resistance to targeted therapies in breast cancer.
Distinctions:
Incumbent Naddisy Foundation Chair in Breast Cancer Research (2023-)
Incumbent Patricia and James Cayne Chair for Junior Faculty (2022-2023)
Section Head for Translational Research in Breast Cancer (2019-)
Scientific Advisory Board Member (2019-) including Chair (2023-2025) – Breast Cancer Research Foundation
Member, American Society of Clinical Investigation
