Brett Carver, MD, PhD

Associate Attending

Brett Carver

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My research focuses on identifying genetic and molecular alterations associated with prostate cancer, studying molecular pathways responsible for initiating the disease and causing its progression, and developing ways to translate these findings into preclinical studies and clinical trials.

In 2010, we published the largest data set of the comprehensive profiling of prostate cancer through a multidisciplinary collaboration at Memorial Sloan Kettering. From this work, we were able to identify a number of novel genetic alterations that are currently being evaluated to determine their precise role in the biology of prostate tumorigenesis.

We are investigating the rational development of combination therapy to treat prostate cancer, particularly castrate-resistant prostate cancer. Given ample evidence that loss of the tumor suppressor PTEN leads to activation of the PI3K pathway, we have developed a number of novel therapies targeting this pathway.

We recently demonstrated that the PI3K and AR pathways cross-regulate each other by reciprocal feedback whereby inhibition of one activates the other, maintaining tumor cell survival. We showed that combined inhibition of PI3K and AR signaling caused near-complete prostate cancer regression in PTEN-deficient mouse models and in human prostate cancer xenografts. We also have developed in vitro and in vivo preclinical models of acquired resistance to combined PI3K and AR pathway inhibition and are currently exploring the mechanisms of resistance.

In collaboration with Howard I. Scher, Chief of the Genitourinary Oncology Service, we are testing combined inhibition of PI3 and AR pathways in castration-resistant prostate cancer in phase II clinical trials. I assist with trial design and secondary molecular analyses of patient specimens, with the goals of evaluating target inhibition, feedback pathway regulation, and mechanisms of resistance. We hope this model will serve as a platform for future trials investigating novel targeted therapies in prostate cancer.