Androgen annihilation as a new therapeutic paradigm in advanced prostate cancer

PURPOSE OF REVIEW: Treatment of all stages of prostate cancer has changed considerably in recent years, as our understanding of its biochemical pathways has improved. Testosterone, true to Huggins original observation, remains a key player not only in newly diagnosed prostate cancer but also in castration-resistant prostate cancer, and our understanding of how to combine and sequence drugs that attack these pathways continues to grow. New US Food and Drugs Administration approved pharmaceutical agents further eliminate testosterone ligand or its activity via inhibition of key synthetic enzymes and through strong inhibition of the androgen receptor. RECENT FINDINGS: This review will briefly examine our knowledge of the complex relationship between testosterone, androgen receptor and advanced prostate cancer, discuss the limits of traditional androgen deprivation therapy in the form of gonadotropin- releasing hormone agonists and newer antagonists, examine combination therapies, including combined androgen blockade and newer studies with 5α-reductase inhibitors, and overview two new therapeutics that target hormonal pathways. SUMMARY: This review provides guidance on trials that examine combination therapies in various prostate cancer disease states. Androgens and prostate cancer remain inexorably linked, and this review will shed light on renewed focus on eliminating activity of this trophic ligand. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.