Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer TherapyReport as inadecuate


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


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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

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





Author: Vito Cucchiara 1,2, Joy C. Yang 1, Vincenzo Mirone 2, Allen C. Gao 1,4, Michael G. Rosenfeld 3 and Christopher P. Evans 1,4,*

Source: http://mdpi.com/



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