title: [How to manage patients with CRPC?].
abstract: Despite castrate levels of androgens, the androgen receptor (AR) remains active and continues to drive prostate cancer progression. Since the approval of docetaxel, four additional agents that show a survival benefit have been registered on the basis of randomized phase 3 trials. These have included enzalutamide and abiraterone, two agents designed specifically to affect the androgen axis, sipuleucel-T, which stimulates the immune system and cabazitaxel, a chemotherapeutic agent. Denosumab was shown to significantly delay skeletal-related events. Clinicians are challenged with a multitude of treatment options and potential sequencing of these agents that, consequently, make clinical decision making more complex. The induction of constitutively-active AR splice variants (AR-Vs) driving clonal proliferation of AR-negative and AR-independent metastases may be one major potential mechanism of resistance to new hormone therapies.
authors.affiliation: Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France. Electronic address: philippe.beuzeboc@curie.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Beuzeboc
authors.affiliation: Institut Gustave-Roussy, département d'oncologie médicale, 94076 Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
mesh_terms: D000069501:Abiraterone Acetate; D000736:Androstenes / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001549:Benzamides; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D017326:Clinical Trials, Phase III as Topic; D000069448:Denosumab; D000077143:Docetaxel; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use; D014020:Tissue Extracts / Q000627:therapeutic use
chemical_list: D000736:Androstenes; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D043823:Taxoids; D014020:Tissue Extracts; D000077143:Docetaxel; D010669:Phenylthiohydantoin; D000069448:Denosumab; C552428:cabazitaxel; C511774:sipuleucel-T; C540278:enzalutamide; D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: AR-V7; Abiraterone acetate; Acétate d’abiratérone; Alpharadin; Cabazitaxel; Cancer de prostate résistant à la castration; Denosumab; Docetaxel; Docétaxel; Dénosumab; Enzalutamide; Metastatic castration-resistant prostate cancer; Sipuleucel-T; Splicing variants; Variants épissage