Metastatic castration-resistant prostate cancer: time for innovation.
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.
['Tucci|Marcello|M|', 'Scagliotti|Giorgio Vittorio|GV|', 'Vignani|Francesca|F|']
D000736:Androstenes D061067:Antibodies, Monoclonal, Humanized D001549:Benzamides D017326:Clinical Trials, Phase III as Topic D000069448:Denosumab D019008:Drug Resistance, Neoplasm D006801:Humans D008297:Male D009570:Nitriles D010669:Phenylthiohydantoin D064129:Prostatic Neoplasms, Castration-Resistant D011868:Radioisotopes D011883:Radium D011944:Receptors, Androgen D015398:Signal Transduction D043823:Taxoids D014020:Tissue Extracts
castration-resistant prostate cancer immunotherapy bone-targeting agents chemotherapy endocrine therapy