Mechanisms of the development of androgen independence in prostate cancer

World J Urol. 2005 Feb;23(1):1-9. doi: 10.1007/s00345-004-0473-1. Epub 2005 Jan 27.


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.

Publication types

  • Review

MeSH terms

  • Androgens / metabolism*
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Humans
  • Male
  • Mutation
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogenes / genetics
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Treatment Outcome


  • Androgens
  • Antineoplastic Agents
  • Receptors, Androgen