Strategies for targeting the androgen receptor axis in prostate cancer.

Androgen receptor (AR) signaling plays a critical role in prostate cancer cell proliferation, survival, and differentiation. Therapeutic strategies targeting the androgen receptor have been developed for the treatment of metastatic hormone-naïve prostate cancer; however, despite effective targeting recent studies have demonstrated that during progression to a castrate-resistant phenotype there is restoration of AR target gene expression. On the basis of this observation, second-generation therapeutics have been developed to target AR in the castrate-resistant setting resulting in a survival benefit. In this review we will discuss the mechanisms promoting AR signaling and the development of second-generation therapeutics targeting AR in castrate-resistant prostate cancer.