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Neil Vasan, MD, PhD
Medical Oncology Fellow
Memorial Sloan Kettering Cancer Center
New York, New York
Conquer Cancer Foundation of ASCO
- Seeking to improve response to targeted therapies in ER-positive breast cancer.
- Laboratory studies are conducted to identify patients most likely to respond to PI3K-targeted therapy.
- This preclinical work may provide the foundation for clinical trials for PI3K inhibitors in selected breast cancer patients.
The PI3K pathway is a robust growth pathway that is frequently dysregulated in ER-positive breast cancers. In spite of its role in tumor growth, drugs that target this pathway have been largely unsuccessful in clinical trials. Dr. Neil believes that newly discovered mutations in the genes that regulates PI3K may identify patients most likely to respond to anti-PI3K therapy.
Full Research Summary
One of the most common mutations that occurs in breast cancers that are driven by the hormone estrogen (called ER-positive) is in the PIK3CA gene. This gene controls a potent growth pathway called PI3K. Inhibitors of PI3K are in clinical trials in breast cancer and patients with mutations in PIK3CA respond better to these drugs than those without a mutation. However, not all patients with a PIK3CA mutation respond to the targeted therapy and the reasons for this are not well understood.
Recent work by Dr. Neil’s group identified frequent dual mutations in the PIK3CA gene. If the dual mutation is more potent in promoting tumor growth it could serve as a marker of response to PI3K inhibitors.
In his Conquer Cancer Foundation study supported by BCRF, Dr. Neil will test this idea by comparing the effects of the dual PIK3CA mutation vs. single mutation on activity of the PI3K pathway, tumor formation and response to PI3K inhibitors in laboratory models of breast cancer.
Results from this study may show that breast tumors bearing two PIK3CA mutations are particularly dependent on the PI3K pathway to survive, and consequently are exquisitely sensitive to PI3K inhibitors. Most importantly, this could provide rationale for a clinical trial of PI3K inhibitors in patients with dual PIK3CA mutations
Neil Vasan, MD, PhD, is a third year Medical Oncology fellow at Memorial Sloan Kettering Cancer Center. He completed his AB/AM at Harvard University, MD/PhD at Yale University School of Medicine, and Residency in Internal Medicine at Massachusetts General Hospital. He short tracked into fellowship at MSKCC, where he served as Chief Fellow during 2016-17. His research focuses on mechanisms of sensitivity and resistance to PI3K inhibitors in breast cancer. He is a member of the ASCO Trainee Council, the ASCO University Review Panel, and the AACR Associate Member Council. He looks forward to a physician scientist career in breast oncology.