Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate CancerReportar como inadecuado


Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate Cancer


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1

Department of Urology, Nihon University School of Medicine, Tokyo 173-8610, Japan

2

Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan

3

Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan





*

Author to whom correspondence should be addressed.



Academic Editor: Emmanuel S. Antonarakis

Abstract Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor AR. Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer CRPC. Surprisingly, AR and the AR signaling pathway are still activated in most CRPC cases. To overcome this problem, abiraterone acetate and enzalutamide were introduced for the treatment of CRPC. Despite the impact of these drugs on prolonged survival, CRPC acquires further resistance to keep the AR pathway activated. Functional molecular studies have shown that some of the AR collaborative transcription factors TFs, including octamer transcription factor OCT1, GATA binding protein 2 GATA2 and forkhead box A1 FOXA1, still stimulate AR activity in the castration-resistant state. Therefore, elucidating the crosstalk between the AR and collaborative TFs on the AR pathway is critical for developing new strategies for the treatment of CRPC. Recently, many compounds targeting this pathway have been developed for treating CRPC. In this review, we summarize the AR signaling pathway in terms of AR collaborators and focus on pyrrole-imidazole PI polyamide as a candidate compound for the treatment of prostate cancer. View Full-Text

Keywords: androgen receptor; androgen receptor signaling pathway; coregulator; octamer transcription factor 1; pyrrole-imidazole polyamide androgen receptor; androgen receptor signaling pathway; coregulator; octamer transcription factor 1; pyrrole-imidazole polyamide





Autor: Daisuke Obinata 1,2, Kenichi Takayama 2, Satoru Takahashi 1 and Satoshi Inoue 2,3,*

Fuente: http://mdpi.com/



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