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Mapping Synthetic Lethal Relationships Between Oncogenes and Small Molecules

Project: Mapping Synthetic Lethal Relationships Between Oncogenes and Small Molecules

Principal Investigator - Sourav Bandyopadhyay

ABSTRACT

Cancer is driven by mutations in oncogenes and tumor suppressors. In breast cancer, activating mutations in an oncogene such as PIK3CA, EGFR, HER2 or inactivation of tumor suppressors P53 or Rb are evident in nearly every tumor. For a some genes such as HER2 and EGFR, mutation in these oncogenes are used as markers for personalized drug treatments targeting these mutant oncogenes which tumors depend on for growth and survival.

Beyond a few key examples the influence of aberrant oncogene activation on patient drug responses is almost completely unknown. To address this issue we are developing technologies to measure the influence of a panel oncogenic kinases in breast cancer on the susceptibility to ~100 anti-cancer drugs. The aim of these studies is to derive a chemical-genetic interaction map that can guide the selection of personalized therapeutic regimens based on selected patient biomarkers. Our efforts are supported by valuable collaborations at UCSF in the interrogation of mechanistic insights from our screens (Frank McCormick), identification of clinically relevant markers (Andrei Goga), and query of patient signatures in ongoing clinical trials (Laura Van’t Veer).