Table of Contents
Advances in Andrology
Volume 2014, Article ID 748352, 9 pages
Review Article

Looking beyond Androgen Receptor Signaling in the Treatment of Advanced Prostate Cancer

1Department of Molecular and Cellular Biochemistry and the Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, OH 43210, USA
2Ohio State Biochemistry Graduate Program, The Ohio State University, Columbus, OH 43210, USA

Received 19 January 2014; Accepted 17 March 2014; Published 10 April 2014

Academic Editor: Wen-Chin Huang

Copyright © 2014 Benjamin Sunkel and Qianben Wang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


This review will provide a description of recent efforts in our laboratory contributing to a general goal of identifying critical determinants of prostate cancer growth in both androgen-dependent and -independent contexts. Important outcomes to date have indicated that the sustained activation of AR transcriptional activity in castration-resistant prostate cancer (CRPC) cells results in a gene expression profile separate from the androgen-responsive profile of androgen-dependent prostate cancer (ADPC) cells. Contributing to this reprogramming is enhanced FoxA1 recruitment of AR to G2/M phase target gene loci and the enhanced chromatin looping of CRPC-specific gene regulatory elements facilitated by PI3K/Akt-phosphorylated MED1. We have also observed a role for FoxA1 beyond AR signaling in driving G1/S phase cell cycle progression that relies on interactions with novel collaborators MYBL2 and CREB1. Finally, we describe an in-depth mechanism of GATA2-mediated androgen-responsive gene expression in both ADPC and CRPC cells. Altogether these efforts provide evidence to support the development of novel prostate cancer therapeutics that address downstream targets of AR activity as well as AR-independent drivers of disease-relevant transcription programs.