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Molecular Indicators of Castration-Resistant Prostate Cancer

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Technical Report,30 Sep 2012,29 Sep 2015

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Johns Hopkins University Baltimore United States

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Metastatic prostate cancers are commonly treated by agents designed to suppress androgen receptor AR signaling mediated by the full-length AR AR-FL. Why some patients progress rapidly after treatment while others benefit with prolonged remission is an unsolved question. We propose approaches to develop molecular indicators of response and resistance that will enable prediction before therapy or early detection during therapy of therapeutic benefit. We will test the hypothesis that AR splice variants AR-Vs are molecular indicators of castration-resistant prostate cancer CRPC. During the funding period, we achieved major milestones by completing RNA sequencing of 55 clinical specimens and yielding data supporting the clinical importance of AR-V7, by establishing an association of AR-V7 with resistance to two current FDA-approved AR targeting therapies, and by demonstrating the feasibility of serial AR-V7 testing in men undergoing standard-of-care treatments for metastatic CRPC. We conclude that detection of AR-V7 predicts treatment outcome in men with metastatic castration resistant prostate cancer initiating AR-targeting therapies.

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