title: Future directions for the use of hypomethylating agents.
abstract: Epigenetics refers to heritable changes in DNA and chromatin that impact gene expression without a change in DNA sequence. Two major steps involved in epigenetic regulation of gene expression include methylation of the promoter region of the gene and deacetylation of specific lysine residues on promoter-associated histones leading to changes in chromatin structure. Promoter hypermethylation is the most extensively studied epigenetic process. Our expanding knowledge of this process has led to its application in the diagnosis, prognosis, and treatment of various hematologic and neoplastic diseases. Several agents, which reverse promoter methylation or inhibit histone deacetylases, are under development for use alone or in combination for a variety of neoplastic diseases. This review discusses the potential use of methylation reversing agents in the treatment of solid tumors and in benign hematologic disorders along with the rationale for combination therapies using hypomethylating agents.
authors: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ggarciam@mdanderson.org
authors: Guillermo
authors: G
authors: Garcia-Manero
authors: Steven D
authors: SD
authors: Gore
mesh_terms: D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005544:Forecasting; D006402:Hematologic Diseases / Q000188:drug therapy; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D056572:Histone Deacetylase Inhibitors; D015254:DNA Modification Methylases