Modulators of DNA methylation and histone acetylation |
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| Affiliation: | 1. Department of Chemistry, CC.MM, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain;2. Campus of Excellence International ceiA3, University of Huelva, Spain;3. Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain;4. Department Bioquímica, Bromatologia, Toxicología y Medicina Legal, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain;5. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 41013 Seville, Spain;6. Instituto de Biomedicina de Sevilla (IBiS)—Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain;1. Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA;2. Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Rockville, MD, 20892, USA;3. School of Mathematics, Shandong University, Jinan, Shandong, 250100, China |
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| Abstract: | The distribution of epigenetic alterations, such as DNA methylation and histone modifications, is abnormal in cancer cells, and drugs that influence these changes are currently being used effectively in the treatment of hematopoietic malignancies. Two hypomethylating agents, 5-azacytidine and decitabine, are FDA-approved for the treatment of myelodysplastic syndromes, and one histone deacetylase inhibitor, vorinostat, was recently FDA-approved for patients with refractory cutaneous T-cell lymphoma. Generally, these agents are very well tolerated, with myelosuppression being the major side effect. Although they are thought to work by re-organizing chromatin to allow expression of genes silenced by DNA hypermethylation and repressive histone modifications, the precise mechanism of action of these agents is not yet clear. Current studies are examining the utility of these agents for the treatment of solid tumors as well as testing these drugs in combination to treat a variety of malignancies. |
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