title: Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.
abstract: Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets.
authors.affiliation: Department of Urology, School of Medicine, University of California, Davis, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA. vito.cucchiara89@gmail.com.|Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II, Naples 80131, Italy. vito.cucchiara89@gmail.com.
authors.forename: Vito
authors.initials: V
authors.lastname: Cucchiara
authors.affiliation: Department of Urology, School of Medicine, University of California, Davis, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA. jcyang@ucdavis.edu.
authors.forename: Joy C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II, Naples 80131, Italy. mirone@unina.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mirone
authors.affiliation: Department of Urology, School of Medicine, University of California, Davis, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA. acgao@ucdavis.edu.|Comprehensive Cancer Center, UC Davis School of Medicine, University of California, Davis, Sacramento, CA 95817, USA. acgao@ucdavis.edu.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Gao
authors.affiliation: Department of Medicine, Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093, USA. mrosenfeld@ucsd.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
authors.affiliation: Department of Urology, School of Medicine, University of California, Davis, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA. cpevans@ucdavis.edu.|Comprehensive Cancer Center, UC Davis School of Medicine, University of California, Davis, Sacramento, CA 95817, USA. cpevans@ucdavis.edu.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
keywords: acetylation; androgen receptor; biomarkers; epigenetics; methylation; non-coding RNA; novel treatments; prostate cancer