title: The Evolving Biology of Castration-Resistant Prostate Cancer: Review of Recommendations From the Prostate Cancer Clinical Trials Working Group 3.
abstract: In 2008, the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) developed consensus guidelines for clinical trial design and conduct that redefined trial endpoints, with a dual-objective paradigm: to (1) controlling, relieving, or eliminating disease manifestations at the start of treatment; and (2) preventing or delaying further disease manifestations. Clinical and translational research in prostate cancer has expanded our current-day understanding of the mechanisms of its pathogenesis, as well as the different clinicopathologic and molecular subtypes of the disease, and has improved the therapeutic armamentarium for the management of metastatic castration-resistant prostate cancer (CRPC). These new advances led to the development of the updated PCWG3 guidelines in 2015. In this review, we analyze our evolving understanding of the biology of CRPC, acquired resistance mechanisms, and emerging therapeutic targets in light of the updated PCWG3 guidelines. We present a joint perspective from the medical oncology and urologic disciplines on the ongoing efforts to advance clinical trial performance in order to discover new therapies for this fatal disease.
authors.forename: Praveen Ramakrishnan
authors.initials: PR
authors.lastname: Geethakumari
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cookson
authors.forename: William Kevin
authors.initials: WK
authors.lastname: Kelly
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D032921:Consensus; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals