Damon Runyon Researchers

The PI3K/AKT/mTOR signaling pathway normally conveys cues from the cell's environment into programs that promote cellular growth, division, and motility. Components of the PI3K signaling pathway are mutated in greater than 70% of all breast cancers and promote the persistent and exaggerated cell growth that is necessary for tumor formation and survival. This pathway is therefore a promising target for treating breast cancers; however, drugs designed to target the PI3K signaling pathway are initially effective but resistance rapidly develops. Dr. Chandarlapaty [Patterson Trust Clinical Investigator] seeks to understand how tumor cells rapidly adapt to PI3K inhibitor drugs. His initial studies indicate that cancer cells use a cellular mechanism called "negative feedback" to either activate alternative signaling pathways not blocked by the drug or reactivate the PI3K pathway. His goal is to identify other targets that can be blocked in combination with the PI3K pathway to more effectively kill cancer cells but not normal cells. These combinations will be tested in clinical trials in breast cancer patients with mutations in the PI3K pathway. In addition, the Continuation Grant will enable him to pursue studies examining the effects of ER and androgen receptor (AR) activation and signaling in breast and prostate cancers.