title: Translating scientific advancement into clinical benefit for castration-resistant prostate cancer patients.
abstract: In the past 12 months, three novel therapeutics-sipuleucel-T, cabazitaxel, and abiraterone acetate-were granted Food and Drug Administration regulatory approval for the treatment of metastatic castration-resistant prostate cancer (CRPC) patients based on phase III studies that showed a survival advantage. Other agents, including the novel antiandrogen MDV3100, are at an advanced stage of clinical phase III evaluation. The treatment paradigm for CRPC has now changed significantly, and this has introduced new challenges for physicians, including selecting patients for specific therapies, developing the best sequencing and combination regimens for the several new effective agents that have recently been approved or are in development, and dissecting mechanisms of resistance that will inform the development of a new generation of therapeutics. This Focus issue reviews the results obtained with immunotherapies, taxane cytotoxics, and androgen receptor targeting therapeutics for CRPC, as well as the postulated mechanisms of resistance to these protocols and proposed strategies for improvement. The use of biomarkers for patient selection, monitoring of treatment activity, and acceleration of drug approval will be critical for achieving further improvements in the treatment for CRPC, and is also discussed in detail.
authors.affiliation: Section of Medicine, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, Sutton, United Kingdom. Gerhardt.attard@icr.ac.uk
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D057170:Translational Research, Biomedical / Q000639:trends
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel