Outsmarting androgen receptor: creative approaches for targeting aberrant androgen signaling in advanced prostate cancer. Issue 3 (May 2011)

• Record Type: Journal Article
• Authors: Knudsen, Karen E; Kelly, William Kevin
• Is Part Of: Expert review of endocrinology & metabolism. Volume 6:Issue 3(2011)
• Page Start: 483
• Page End: 493
• Publication Date: 2011-05
• Subjects: abiraterone -- androgen receptor -- cell cycle -- hormone therapy -- prostatic adenocarcinoma -- retinoblastoma; Endocrinology -- Periodicals; Metabolism -- Periodicals; 616.4
• DOI: 10.1586/eem.11.33
• Languages: English
• ISSNs: 1744-6651

Abstract

Prostatic adenocarcinomas are reliant on androgen receptor (AR) activity for survival and progression. Therefore, first-line therapeutic intervention for disseminated disease entails the use of AR-directed therapeutics, achieved through androgen deprivation and direct AR antagonists. While initially effective, recurrent, ''castrate-resistant'' prostate cancers arise, for which there is no durable means of treatment. An abundance of clinical study and preclinical modeling has led to the revelation that restored AR activity is a major driver of therapeutic failure and castrate-resistant prostate cancer development. The mechanisms underpinning AR reactivation have been identified, providing the foundation for a new era of drug discovery and rapid translation into the clinic. As will be reviewed in this article, these creative new ways of suppressing AR show early promise.