title: Androgen annihilation as a new therapeutic paradigm in advanced prostate cancer.
abstract: OBJECTIVE
  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 Huggin's 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Colorado, Anschutz Medical Campus, Division of Urology, Aurora, CO 80045, USA.
authors.forename: Kyle O
authors.initials: KO
authors.lastname: Rove
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D013739:Testosterone