Abstract
Pharmacoepigenomics deals with the influence that epigenetic alterations (DNA methylation, histone modifications, chromatin remodeling, non-coding RNA dysregulation) exert on drug efficacy and safety, and also on the effects that drugs may have on the epigenetic machinery. Genes involved in pharmacogenomics (pathogenic, mechanistic, metabolic, transporter, pleiotropic genes) are also affected by epigenetic modifications conditioning the therapeutic outcome. 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, non-coding RNAs (miRNAs) with potential effects against myelodysplastic syndromes, different types of cancer, and neurodegenerative disorders. These drugs may modify epigenetic functions under normal and pathological conditions. Pharmacogenetic and pharmacoepigenetic studies should be incorporated as routine procedures in the future for the proper evaluation of efficacy and safety issues in drug development and clinical trials.
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