Epigenetic regulation of androgen receptor signaling in prostate cancer

Prostate cancer is the most common cancer in men in the United States, and it is the second leading cause of cancer-related death in American men. The Androgen receptor (AR), a nuclear hormone and transcription factor, is the most therapeutically relevant target in this disease. While most efforts in the clinic are still directed at lowering levels of androgens that activate AR, resistance to androgen deprivation eventually develops, and most prostate cancer deaths are attributable to this castration-resistant form of this disease. Recent work has shed light on the importance of epigenetic events including facilitation of AR signaling by histone-modifying enzymes and also on the role that enzymes such as HDAC6 play in stabilizing AR in prostate cancer cells. Herein, we summarize recent findings on the role of epigenetic enzymes in AR signaling and highlight examples on how interdiction of critical epigenetic enzymes may attenuate AR action in prostate cancer.