title: Clinical development of novel therapeutics for castration-resistant prostate cancer: historic challenges and recent successes.
abstract: There have been more drugs approved by the US Food and Drug Administration for the treatment of castration-resistant prostate cancer in the past 3 years than in the prior 3 decades, with additional drugs on the verge of approval based on the results of recently reported randomized trials. While an improvement in the understanding of the pathogenesis of castration-resistant prostate cancer has undeniably accelerated the transition of novel approaches from "bench to bedside," the recent successes in the treatment of prostate cancer are also a result of the efforts of clinical investigators to redefine the framework in which drugs for castration-resistant disease are evaluated. This review will explore the shifting paradigm in drug development for castration-resistant prostate cancer over the past several decades, and highlight how new definitions, trial designs, and endpoints have facilitated the emergence of new therapies for this challenging disease.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. matthew.galsky@mssm.edu
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Small
authors.forename: Che-kai
authors.initials: CK
authors.lastname: Tsao
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
mesh_terms: D000736:Androstenes; D000737:Androstenols / Q000494:pharmacology / Q000627:therapeutic use; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides; D019496:Cancer Vaccines / Q000494:pharmacology / Q000627:therapeutic use; D002369:Castration / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D000069448:Denosumab; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000628:therapy*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D019275:Radiopharmaceuticals / Q000494:pharmacology / Q000627:therapeutic use; D011883:Radium / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D014020:Tissue Extracts / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000736:Androstenes; D000737:Androstenols; D000813:Anilides; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D019496:Cancer Vaccines; D009570:Nitriles; D011725:Pyridines; D053245:RANK Ligand; D019275:Radiopharmaceuticals; D043823:Taxoids; D014020:Tissue Extracts; C558660:cabozantinib; D010669:Phenylthiohydantoin; D000069448:Denosumab; C552428:cabazitaxel; C511774:sipuleucel-T; C540278:enzalutamide; D020794:Receptor Protein-Tyrosine Kinases; D017430:Prostate-Specific Antigen; C089740:abiraterone; D011883:Radium