Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation

A Perfect Combination for Cancer Therapy

Research output: Contribution to journalArticle

Abstract

Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

Original languageEnglish (US)
JournalAdvances in Cancer Research
DOIs
StateAccepted/In press - 2016

Fingerprint

DNA Methylation
Epigenomics
Histones
Co-Repressor Proteins
Neoplasms
Histone Deacetylase Inhibitors
Acetylation
Genetic Promoter Regions
Methylation
Lysine
Chromatin
Therapeutics
Maintenance
Gene Expression
DNA
Enzymes
Genes

Keywords

  • DNA methyltransferase inhibitors
  • Drug synergy
  • Epigenetic therapy
  • Histone deacetylation and methylation inhibitors
  • Solid tumors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation: A Perfect Combination for Cancer Therapy",
abstract = "Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.",
keywords = "DNA methyltransferase inhibitors, Drug synergy, Epigenetic therapy, Histone deacetylation and methylation inhibitors, Solid tumors",
author = "Cynthia Zahnow and M. Topper and M. Stone and {Murray Stewart}, Tracy and H. Li and Baylin, {Stephen B} and Casero, {Robert A}",
year = "2016",
doi = "10.1016/bs.acr.2016.01.007",
language = "English (US)",
journal = "Advances in Cancer Research",
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T2 - A Perfect Combination for Cancer Therapy

AU - Zahnow, Cynthia

AU - Topper, M.

AU - Stone, M.

AU - Murray Stewart, Tracy

AU - Li, H.

AU - Baylin, Stephen B

AU - Casero, Robert A

PY - 2016

Y1 - 2016

N2 - Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

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