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.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States. Electronic address: zahnoci@jhmi.edu.
authors.forename: C A
authors.initials: CA
authors.lastname: Zahnow
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: M
authors.initials: M
authors.lastname: Topper
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: M
authors.initials: M
authors.lastname: Stone
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: T
authors.initials: T
authors.lastname: Murray-Stewart
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: S B
authors.initials: SB
authors.lastname: Baylin
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: R A
authors.initials: RA
authors.lastname: Casero
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019175:DNA Methylation / Q000235:genetics*; D004357:Drug Synergism; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000627:therapeutic use*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D012313:RNA; D006655:Histone Deacetylases
keywords: DNA methyltransferase inhibitors; Drug synergy; Epigenetic therapy; Histone deacetylation and methylation inhibitors; Solid tumors