Partners in Crime: Deregulation of AR Activity and Androgen Synthesis in Prostate Cancer

Overview

Journal Trends Endocrinol Metab

Specialty Endocrinology

Date 2010 Feb 9

PMID 20138542

Citations 159

Authors

Karen E Knudsen

Trevor M Penning

Affiliations

Soon will be listed here.

Abstract

Prostate cancer remains a leading cause of cancer death, as there are no durable means to treat advanced disease. Treatment of non-organ-confined prostate cancer hinges on its androgen dependence. First-line therapeutic strategies suppress androgen receptor (AR) activity, via androgen ablation and direct AR antagonists, whereas initially effective, incurable, 'castration-resistant' tumors arise as a result of resurgent AR activity. Alterations of AR and/or associated regulatory networks are known to restore receptor activity and support resultant therapy-resistant tumor progression. However, recent evidence also reveals an unexpected contribution of the AR ligand, indicating that alterations in pathways controlling androgen synthesis support castration-resistant AR activity. In this report, the mechanisms underlying the lethal pairing of AR deregulation and aberrant androgen synthesis in prostate cancer progression will be discussed.

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