title: Novel strategies to test biological hypotheses in early drug development for advanced prostate cancer.
abstract: BACKGROUND
  Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic.
  
  
  BACKGROUND
  We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs.
  
  
  CONCLUSIONS
  With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.
authors.affiliation: Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor