title: Metastatic castration-resistant prostate cancer: time for innovation.
abstract: Androgen deprivation is the mainstay of advanced prostate cancer treatment. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). The understanding of the biology of CRPC and the evidence that CRPC still remains driven by androgen receptor signaling led to the discovery of new therapeutic targets. In the last few years, large Phase III trials showed improvements in survival and outcomes and led to the approval of a CYP17 inhibitor (abiraterone), an androgen receptor antagonist (enzalutamide), the taxane cabazitaxel, an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T). This article describes the molecular mechanisms underlying castration resistance, discusses recent and ongoing trials and offers some insights into identifying the best sequence of new drugs.
authors.affiliation: University of Turin, Department of Oncology, S Luigi Hospital, Division of Medical Oncology, Regione Gonzole, 10, 10043 - Orbassano (Torino), Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: Francesca
authors.initials: F
authors.lastname: Vignani
mesh_terms: D000736:Androstenes / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D017326:Clinical Trials, Phase III as Topic; D000069448:Denosumab; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011868:Radioisotopes / Q000627:therapeutic use; D011883:Radium / Q000627:therapeutic use; D011944:Receptors, Androgen / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000627:therapeutic use; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000736:Androstenes; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D009570:Nitriles; D011868:Radioisotopes; D011944:Receptors, Androgen; D043823:Taxoids; D014020:Tissue Extracts; D010669:Phenylthiohydantoin; D000069448:Denosumab; C511774:sipuleucel-T; C540278:enzalutamide; C089740:abiraterone; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: bone-targeting agents; castration-resistant prostate cancer; chemotherapy; endocrine therapy; immunotherapy