title: Translational and clinical implications of the genetic landscape of prostate cancer.
abstract: Over the past several years, analyses of data from high-throughput studies have elucidated many fundamental insights into prostate cancer biology. These insights include the identification of molecular alterations and subtypes that drive tumour progression, recurrent aberrations in signalling pathways, the existence of substantial intertumoural and intratumoural heterogeneity, Darwinian evolution in response to therapeutic pressures and the complicated multidirectional patterns of spread between primary tumours and metastatic sites. However, these concepts have not yet been fully translated into clinical tools to improve prognostication, prediction and personalization of treatment of patients with prostate cancer. The current and future clinical implications of 'omics' level knowledge is not only revolutionizing our understanding of prostate cancer biology, but is also shaping ongoing, and future clinical investigations and practice. In this Review, we summarize these advances, and the remaining challenges surrounding tumour heterogeneity and the ability to overcome treatment resistance are also described.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Spratt
authors.affiliation: Department of Radiation Oncology, Cedars Sinai Medical Center, 8700 Beverly Blvd, West Hollywood, CA 90048, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Zumsteg
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.|Michigan Center for Translational Pathology, University of Michigan Medical School, 1524 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200, Ann Arbor, Michigan, USA.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Department of Pathology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.|Department of Urology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.|Michigan Center for Translational Pathology, University of Michigan Medical School, 1524 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200, Ann Arbor, Michigan, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
mesh_terms: D000728:Androgens / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D018358:Neuroendocrine Tumors / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D014157:Transcription Factors; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human