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Cancers 2017, 9(1), 9; doi:10.3390/cancers9010009

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy

1
Department of Urology, School of Medicine, University of California, Davis, 4860 Y Street, Suite 3500, Sacramento, CA 95817, USA
2
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II, Naples 80131, Italy
3
Department of Medicine, Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093, USA
4
Comprehensive Cancer Center, UC Davis School of Medicine, University of California, Davis, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Emmanuel S. Antonarakis
Received: 30 November 2016 / Revised: 2 January 2017 / Accepted: 11 January 2017 / Published: 16 January 2017
(This article belongs to the Special Issue AR Signaling in Human Malignancies: Prostate Cancer and Beyond)
View Full-Text   |   Download PDF [1343 KB, uploaded 16 January 2017]   |  

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. View Full-Text
Keywords: epigenetics; prostate cancer; androgen receptor; methylation; acetylation; non-coding RNA; biomarkers; novel treatments epigenetics; prostate cancer; androgen receptor; methylation; acetylation; non-coding RNA; biomarkers; novel treatments
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Cucchiara, V.; Yang, J.C.; Mirone, V.; Gao, A.C.; Rosenfeld, M.G.; Evans, C.P. Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy. Cancers 2017, 9, 9.

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