Epigenomic regulation of androgen receptor signaling: Potential role in prostate cancer therapy

Vito Cucchiara, Joy C. Yang, Vincenzo Mirone, Allen C Gao, Michael G. Rosenfeld, Christopher P Evans

Research output: Contribution to journalReview article

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article number9
JournalCancers
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Androgen Receptors
Epigenomics
Prostatic Neoplasms
Castration
Genetic Epigenesis
Therapeutics
Untranslated RNA
DNA Methylation
Pharmaceutical Preparations
Androgens
Chromatin
Carcinogenesis
Biomarkers
Genome
Gene Expression

Keywords

  • Acetylation
  • Androgen receptor
  • Biomarkers
  • Epigenetics
  • Methylation
  • Non-coding RNA
  • Novel treatments
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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.

In: Cancers, Vol. 9, No. 1, 9, 01.01.2017.

Research output: Contribution to journalReview article

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. In: Cancers. 2017 ; Vol. 9, No. 1.
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