title: Molecular alterations and emerging targets in castration resistant prostate cancer.
abstract: Prostate cancer is the most common malignancy in Western Europe, of which approximately 10-20% presents with advanced or metastatic disease. Initial response with androgen deprivation therapy is almost universal, but progression to castration resistant prostate cancer (CRPC), an incurable disease, occurs in approximately 2-3 years. In recent years, the novel taxane cabazitaxel, the hormonal agents abiraterone and enzalutamide, the immunotherapeutic agent sipuleucel-T and the radiopharmaceutical radium-223 have been shown to prolong survival in large randomised trials, thus widely increasing the therapeutic armamentarium against the disease. Despite these advances, the median survival in the first-line setting of metastatic castration-resistant prostate cancer (mCRPC) is still up to 25 months and in the post-docetaxel setting is about 15-18 months. There is an urgent need for the development of biomarkers of treatment response, and for a deeper understanding of tumour heterogeneity and the molecular biology underlying the disease. In this review, we attempt to provide insight into the novel molecular targets showing promise in clinical trials.
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, SM2 5PT Sutton, Surrey, UK.
authors.forename: D
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, SM2 5PT Sutton, Surrey, UK. Electronic address: Johann.De-Bono@icr.ac.uk.
authors.forename: J S
authors.initials: JS
authors.lastname: De Bono
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics*; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: Androgen receptor; Castration resistant prostate cancer; Molecular biology; Novel therapeutics