title: Prostate cancer.
abstract: Much progress has been made in research for prostate cancer in the past decade. There is now greater understanding for the genetic basis of familial prostate cancer with identification of rare but high-risk mutations (eg, BRCA2, HOXB13) and low-risk but common alleles (77 identified so far by genome-wide association studies) that could lead to targeted screening of patients at risk. This is especially important because screening for prostate cancer based on prostate-specific antigen remains controversial due to the high rate of overdiagnosis and unnecessary prostate biopsies, despite evidence that it reduces mortality. Classification of prostate cancer into distinct molecular subtypes, including mutually exclusive ETS-gene-fusion-positive and SPINK1-overexpressing, CHD1-loss cancers, could allow stratification of patients for different management strategies. Presently, men with localised disease can have very different prognoses and treatment options, ranging from observation alone through to radical surgery, with few good-quality randomised trials to inform on the best approach for an individual patient. The survival of patients with metastatic prostate cancer progressing on androgen-deprivation therapy (castration-resistant prostate cancer) has improved substantially. In addition to docetaxel, which has been used for more than a decade, in the past 4 years five new drugs have shown efficacy with improvements in overall survival leading to licensing for the treatment of metastatic castration-resistant prostate cancer. Because of this rapid change in the therapeutic landscape, no robust data exist to inform on the selection of patients for a specific treatment for castration-resistant prostate cancer or the best sequence of administration. Moreover, the high cost of the newer drugs limits their widespread use in several countries. Data from continuing clinical and translational research are urgently needed to improve, and, crucially, to personalise management.
authors.affiliation: Division of Clinical Studies, The Institute of Cancer Research, London, UK; Prostate Cancer Targeted Therapy Group, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.affiliation: Academic Urology Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
authors.affiliation: Clinical Academic Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK; Oncogenetics Team, Division of Cancer Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
authors.forename: Ros A
authors.initials: RA
authors.lastname: Eeles
authors.affiliation: Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Fritz
authors.initials: F
authors.lastname: Schröder
authors.affiliation: Departments of Pathology Urology, Comprehensive Cancer Center and Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.affiliation: Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Tannock
authors.affiliation: Division of Medical Oncology, Johns Hopkins Hospital, Baltimore, MA, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Drake
authors.affiliation: Division of Clinical Studies, The Institute of Cancer Research, London, UK; Prostate Cancer Targeted Therapy Group, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK. Electronic address: jdebono@icr.ac.uk.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D055088:Early Detection of Cancer; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D051059:PTEN Phosphohydrolase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D004265:DNA Helicases; C080359:CHD1 protein, human