title: Targeting continued androgen receptor signaling in prostate cancer.
abstract: Prostate cancer is the most common cancer and the second leading cause of death from cancer in males in most Western countries. Prostate cancer has an exquisite sensitivity to androgen deprivation therapy and is the most endocrine-sensitive solid neoplasm, although advanced disease eventually progresses to castration-resistant prostate cancer (CRPC). Recent evidence has shown that cancer progression at the CRPC stage is often mediated by androgen receptor signaling, so that subsequent androgen receptor targeting may further contribute to disease control and, eventually, survival improvement. Abiraterone acetate, an androgen biosynthesis inhibitor, was tested in patients with CRPC pretreated with docetaxel in a phase III trial with demonstration of an overall survival benefit, confirming that CRPC remains hormone driven, even in advanced stages of the disease. Several novel agents also targeting androgen receptor signaling are currently being evaluated, including MDV3100 and orteronel (TAK-700). With the availability of newer endocrine treatments and also nonendocrine treatments (e.g., chemotherapy, immunotherapy, and bone-targeting agents), data supporting a more rational use of therapeutic agents are urgently required in patients with CRPC. It is likely that molecular characterization of prostate cancer will lead to the identification of different subsets of prostate cancer disease with a different natural history, sensitivity, and resistance to treatment; efforts to develop, validate, and implement predictive biomarkers in clinical trials and eventually in routine care should now be strongly supported.
authors.affiliation: Institut Gustave Roussy, Department of Cancer Medicine, University of Paris Sud, Unité INSERM U981, Paris, France. christophe.massard@igr.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009919:Orchiectomy; D057285:Precision Medicine; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D011944:Receptors, Androgen