Preclinical Studies of Signaling Pathways in a Mutant Mouse Model of Hormone-Refractory Prostate Cancer

We have been investigating targeted therapies for the treatment of advanced prostate cancer using a genetically-engineered mouse model of the disease. We performed pre-clinical studies to examine the consequences of combinatorial inhibition of these signaling pathways using Rapamycin, an inhibitor of mTOR, and PD0325901, a MEK inhibitor, is potently anti-tumorigenic in mouse models of castration-resistant prostate cancer. Current studies reported herein demonstrate that this combination is also effective for tumor suppression of advanced prostate cancer models and can improve survival. Studies in progress are evaluating new combinations and also evaluating molecular changes in response to therapy.
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