title: Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate Cancer.
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.
authors.affiliation: Department of Urology, Nihon University School of Medicine, Tokyo 173-8610, Japan. obinata.daisuke@nihon-u.ac.jp.|Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. obinata.daisuke@nihon-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Obinata
authors.affiliation: Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. ktakayama-tky@umin.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Urology, Nihon University School of Medicine, Tokyo 173-8610, Japan. takahashi.satoru@nihon-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. sinoue@tmig.or.jp.|Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan. sinoue@tmig.or.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
keywords: androgen receptor; androgen receptor signaling pathway; coregulator; octamer transcription factor 1; pyrrole-imidazole polyamide