title: Mechanisms of the development of androgen independence in prostate cancer.
abstract: The effectiveness of androgen ablation in the management of advanced prostate cancer is of limited duration, with the median length of response being only 18-24 months. The transition of the prostate cancer cell to an androgen independent phenotype is a complex process that involves selection and outgrowth of pre-existing clones of androgen-independent cells (clonal selection) as well as adaptive up-regulation of genes that help the cancer cells survive and grow after androgen ablation (adaptation). These two mechanisms share an important pre-requisite characteristic: prostate cancers are heterogeneous tumours comprised of various subpopulations of cells that respond differently to androgen withdrawal therapy. This tumour heterogeneity may reflect either a multifocal origin, adaptation to environmental stimuli, and/or genetic instability of the initial cancer. This review will reexamine the different mechanisms that enable prostate cancer cells to proliferate in an androgen depleted environment.
authors.affiliation: The Prostate Centre, Vancouver General Hospital, University of British Columbia, 2660 Oak Street, BC V6H 3Z6, Vancouver, Canada. aso@vanhosp.bc.ca
authors.forename: Alan
authors.initials: A
authors.lastname: So
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado-Col
authors.forename: Colleen
authors.initials: C
authors.lastname: Nelson
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011519:Proto-Oncogenes / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D011944:Receptors, Androgen