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World J Urol. 2005 Feb;23(1):1-9. Epub 2005 Jan 27.

Mechanisms of the development of androgen independence in prostate cancer.

Author information

1
The Prostate Centre, Vancouver General Hospital, University of British Columbia, 2660 Oak Street, BC V6H 3Z6, Vancouver, Canada. aso@vanhosp.bc.ca

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.

PMID:
15770516
DOI:
10.1007/s00345-004-0473-1
[Indexed for MEDLINE]

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