The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

Edwards, J. and Bartlett, J.M.S. (2005) The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor. BJU International, 95(9), pp. 1320-1326. (doi: 10.1111/j.1464-410X.2005.05526.x)

Abstract

Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance.

• Item Type: Articles
• Additional Information: The definitive version is available at www.blackwell-synergy.com
• Keywords: Androgen receptor, hormone resistance, MAP kinase, PI3K and PKC
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Edwards, Professor Joanne
• Authors: Edwards, J., and Bartlett, J.M.S.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: BJU International
• Journal Abbr.: BJU Int.
• Publisher: Wiley-Blackwell
• ISSN: 1464-4096
• ISSN (Online): 1464-410X
• Published Online: 12 May 2005
• Copyright Holders: Copyright © 2005 Wiley-Blackwell
• First Published: First published in British Journal of Urology International 95(9):1320-1326
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.