title: Epigenomic networking in drug development: from pathogenic mechanisms to pharmacogenomics.
abstract: Different epigenetic alterations (DNA methylation, histone modifications, chromatin remodeling, noncoding RNA dysregulation) are associated with the phenotypic expression of complex disorders in which genomic, epigenomic, proteomic, and metabolomic changes, in conjunction with environmental factors, are involved. As epigenetic modifications are reversible and can be potentially targeted by pharmacological and dietary interventions, a series of epigenetic drugs have been developed, including DNA methyltransferase inhibitors (nucleoside analogs, small molecules, bioproducts, antisense oligonucleotides, miRNAs), histone deacetylase inhibitors (short-chain fatty acids, hydroxamic acids, cyclic peptides, benzamides, ketones, sirtuin inhibitors, sirtuin activators), histone acetyltransferase modulators, histone methyltransferase inhibitors, histone demethylase inhibitors, and noncoding RNAs (miRNAs), with potential effects against myelodysplastic syndromes, different types of cancer, and neurodegenerative disorders. Pharmacogenetic and pharmacoepigenetic studies are required for the proper evaluation of efficacy and safety issues in clinical trials with epigenetic drugs.
authors.affiliation: Genomic Medicine, Camilo José Cela University, Madrid, 28692, Spain; EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Corunna, 15165, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D019175:DNA Methylation; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods*
chemical_list: D004791:Enzyme Inhibitors; D035683:MicroRNAs
keywords: DNA methyltransferase inhibitors; epigenetic drugs; epigenetics; histone acetyltransferase activators; histone deacetylase (HDAC) inhibitors; histone demethylase inhibitors; histone methyltransferase inhibitors; miRNAs; non-coding RNAs; pharmacogenetics