Cargando…

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

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 resis...

Descripción completa

Detalles Bibliográficos
Autores principales: Cucchiara, Vito, Yang, Joy C., Mirone, Vincenzo, Gao, Allen C., Rosenfeld, Michael G., Evans, Christopher P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295780/
https://www.ncbi.nlm.nih.gov/pubmed/28275218
http://dx.doi.org/10.3390/cancers9010009
_version_ 1782505497090326528
author Cucchiara, Vito
Yang, Joy C.
Mirone, Vincenzo
Gao, Allen C.
Rosenfeld, Michael G.
Evans, Christopher P.
author_facet Cucchiara, Vito
Yang, Joy C.
Mirone, Vincenzo
Gao, Allen C.
Rosenfeld, Michael G.
Evans, Christopher P.
author_sort Cucchiara, Vito
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5295780
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-52957802017-02-08 Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy Cucchiara, Vito Yang, Joy C. Mirone, Vincenzo Gao, Allen C. Rosenfeld, Michael G. Evans, Christopher P. Cancers (Basel) Review 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. MDPI 2017-01-16 /pmc/articles/PMC5295780/ /pubmed/28275218 http://dx.doi.org/10.3390/cancers9010009 Text en © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Cucchiara, Vito
Yang, Joy C.
Mirone, Vincenzo
Gao, Allen C.
Rosenfeld, Michael G.
Evans, Christopher P.
Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy
title Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy
title_full Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy
title_fullStr Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy
title_full_unstemmed Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy
title_short Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy
title_sort epigenomic regulation of androgen receptor signaling: potential role in prostate cancer therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295780/
https://www.ncbi.nlm.nih.gov/pubmed/28275218
http://dx.doi.org/10.3390/cancers9010009
work_keys_str_mv AT cucchiaravito epigenomicregulationofandrogenreceptorsignalingpotentialroleinprostatecancertherapy
AT yangjoyc epigenomicregulationofandrogenreceptorsignalingpotentialroleinprostatecancertherapy
AT mironevincenzo epigenomicregulationofandrogenreceptorsignalingpotentialroleinprostatecancertherapy
AT gaoallenc epigenomicregulationofandrogenreceptorsignalingpotentialroleinprostatecancertherapy
AT rosenfeldmichaelg epigenomicregulationofandrogenreceptorsignalingpotentialroleinprostatecancertherapy
AT evanschristopherp epigenomicregulationofandrogenreceptorsignalingpotentialroleinprostatecancertherapy