New Therapies for Prostate Cancer Based on the Biology of Androgen Receptor Coregulators

Prostate cancer is currently the most prevalent cancer among men in the United States and ranks second to lung cancer in terms of annual mortality. The androgen receptor (AR) is central to the initiation and growth of prostate cancer and to the therapeutic response to hormones. Although it has been known for many years that the expression and activity of AR is controlled by AR coregulators, the manipulation of endogenous AR coregulators to affect AR levels or function has not been widely exploited clinically. Coregulators are proteins that interact with AR to either enhance (coactivators) or reduce (corepressors) transcriptional activity. They act via a variety of mechanisms that provide potential therapeutic targets. The purpose of this article is to review the evidence for the deregulated expression and activity of AR associated coregulators in the progression of prostate cancer. The therapeutic use of these coregulators in both clinical and preclinical models is discussed with the aim of suggesting new modalities for prostate cancer treatment.