title: Novel drugs targeting the androgen receptor pathway in prostate cancer.
abstract: After decades of limited success in the treatment of castration-resistant prostate cancer (CRPC), five novel therapeutics were granted Food and Drug Administration regulatory approval in the last 4 years based on several randomized phase III studies that have reported a survival benefit. Among them, two drugs targeting the androgen receptor pathway, namely abiraterone acetate and enzalutamide, have demonstrated that targeting androgen signalling following progression to classical androgen blockade continues to be an effective strategy despite the emergence of resistance mechanisms to sequential treatments. In addition to these two approved drugs, several other promising agents that block steroidogenesis interact with the androgen receptor or modulate post-receptor signal transduction that are undergoing clinical evaluation. This issue reviews the current data and the state of development of novel androgen receptor-targeting drugs and further discusses how this revolution in therapeutic armamentarium for the treatment of CRPC has raised challenges for clinicians about the optimal usage of these compounds.
authors.affiliation: Drug Development Unit, Division of Cancer Therapeutics and Division of Clinical Studies, The Royal Marsden NHS Foundation Trust - The Institute of Cancer Research, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Mateo
authors.forename: Alan
authors.initials: A
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Ong
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen