Review
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World J Clin Urol. Nov 24, 2014; 3(3): 264-271
Published online Nov 24, 2014. doi: 10.5410/wjcu.v3.i3.264
Review of novel therapeutic medicines targeting androgen signaling in castration-resistant prostate cancer
Daisuke Obinata, Kyoko Fujiwara, Kenya Yamaguchi, Ken-ichi Takayama, Tomohiko Urano, Hiroki Nagase, Satoshi Inoue, Satoru Takahashi, Noboru Fukuda
Daisuke Obinata, Kenya Yamaguchi, Satoru Takahashi, Department of Urology, Nihon University School of Medicine, Tokyo 173-8610, Japan
Kyoko Fujiwara, Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
Ken-ichi Takayama, Tomohiko Urano, Satoshi Inoue, Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Hiroki Nagase, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan
Noboru Fukuda, Division of Life Science, Advanced Research Institute of Sciences and Humanities, Nihon University, Tokyo 173-8610, Japan
Author contributions: Obinata D, Fujiwara K, Yamaguchi K, Takayama K, Urano T, Nagase H, Inoue S, Takahashi S and Fukuda N contributed to this paper.
Correspondence to: Noboru Fukuda, MD, PhD, Division of Life Science, Advanced Research Institute of Sciences and Humanities, Nihon University, 30-1 Ooyaguchikamimachi, Itabashi, Tokyo 173-8610, Japan. fukuda.noboru@nihon-u.ac.jp
Telephone: +81-3-39728111 Fax: +81-3-39728666
Received: April 28, 2014
Revised: June 26, 2014
Accepted: July 27, 2014
Published online: November 24, 2014
Processing time: 204 Days and 18.9 Hours
Abstract

Prostate cancer is the most common male malignant neoplasm. Androgens and the androgen receptor (AR) play a key role in the onset and progression of prostate cancer. The expression of the AR is still preserved in the majority of patients with castration-resistant prostate cancer (CRPC). CRPC is considered to be induced by the following mechanisms: (1) sustained AR activation by enhancing intracellular conversion of adrenal androgens to dehydrotestosterone via a de novo route; (2) AR hypersensitivity; (3) promiscuous activation of AR signaling; and (4) outlaw pathways. Recent advances in the treatment of CRPC include novel medicines targeting AR signaling pathways. In addition, functional molecular studies have shown that some of the AR-regulated genes and AR coregulators are prognostic markers and potential therapeutic targets for prostate cancer, particularly in the castration-resistant state. Therefore, identification of the AR signaling pathways responsible for establishment of CRPC is critical for developing new strategies for the treatment of CRPC.

Keywords: Androgen receptor; Prostate cancer; Pyrrole-imidazole polyamide

Core tip: Prostate cancer is the most common male malignant neoplasm. Androgens and the androgen receptor (AR) play a key role in the onset and progression of prostate cancer. The expression of the AR is still preserved in the majority of patients with castration-resistant prostate cancer (CRPC). Therefore, identification of the AR signaling pathways responsible for establishment of CRPC is critical for developing new strategies for the treatment of CRPC.