Manipulation of androgens and alterations in the androgen receptor axis in prostate cancer.

Androgens play a key role in prostate cancer (PCa) development and progression. For decades, androgen deprivation therapy (ADT) has been the primary treatment for men with metastatic prostate cancer. ADT initially results in the regression of prostate cancers, however, this effect is limited and patients inevitably develop an androgen refractory form of the disease. Many studies have implicated the androgen receptor (AR), the key mediator of androgen action, as an important player in PCa recurrence. Changes such as AR gene amplification, AR mutations, and in AR subcellular localization, and AR coregulator status that result in the upregulation of AR activity are often associated with androgen refractory prostate cancers. This review seeks to highlight some of the changes in the AR axis in androgen refractory tumors and the recent advances in ADT. A greater understanding of the AR axis will provide a basis for improving existing methods and developing new methods for the treatment of prostate cancer.