Overcoming castration resistance in prostate cancer

Recent advances in our understanding of the androgen axis signaling pathway have led to the development of therapeutic strategies to overcome the state of 'castration resistance' in prostate cancer. In this review, we examine the mechanisms of castration resistance, as well as recently reported and ongoing clinical studies, which will further identify therapeutic opportunities for novel therapeutics targeting the androgen-signaling axis in advanced prostate cancer.

As evidenced by recently reported positive phase III clinical trials, secondary hormonal agents such as abiraterone and MDV3100 may still be very effective in the treatment of castration-resistant prostate cancer, even after the use of docetaxel chemotherapy.

Novel agents targeting this pathway have demonstrated a proof of principle that overcoming castration resistance is possible, leading to significant changes in the landscape of treatment in this disease. The optimal combination, sequence, and pattern of use in these novel therapies will be the focus of clinical research in the near future.