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Abstract

Volume 11, Issue 1 (January 2009) 11, 69–73; 10.1038/aja.2008.14

The androgen receptor in hormone-refractory prostate cancer

Hai-Lei Mao1,2, Zhi-Qi Zhu1 and Charlie Degui Chen1

1 State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2 Affiliated Hospital of Nantong University, Nantong 226001, China

Correspondence: Dr Charlie Degui Chen, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Fax: + 86-21-5492-1148 E-mail: cdchen@sibs.ac.cn

Received 23 September 2008; Accepted 24 September 2008; Published online 1 December 2008

Abstract

Advanced prostate cancer is responsive to hormone therapy that interferes with androgen receptor (AR) signalling. However, the effect is short-lived, as nearly all tumours progress to a hormone-refractory (HR) state, a lethal stage of the disease. Intuitively, the AR should not be involved because hormone therapy that blocks or reduces AR activity is not effective in treating HR tumours. However, there is still a consensus that AR plays an essential role in HR prostate cancer (HRPC) because AR signalling is still functional in HR tumours. AR signalling can be activated in HR tumours through several mechanisms. First, activation of intracellular signal transduction pathways can sensitize the AR to castrate levels of androgens. Also, mutations in the AR can change AR ligand specificity, thereby allowing it to be activated by non-steroids or anti-androgens. Finally, overexpression of the wild-type AR sensitizes itself to low concentrations of androgens. Therefore, drugs targeting AR signalling could still be effective in treating HRPC.

Keywords: prostate cancer, hormone therapy, androgen receptor, hormone-refractory prostate cancer

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