Ahypomethylating agent (or demethylating agent[1]) is a drug that inhibitsDNA methylation: the modification of DNA nucleotides by addition of a methyl group. Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, treatment with a hypomethylating agent is considered a type ofepigenetic therapy.
Currently available hypomethylating agents block the activity ofDNA methyltransferase (DNA methyltransferase inhibitors / DNMT inhibitors).Currently two members of the class,azacitidine anddecitabine, are FDA-approved for use in the United States inmyelodysplastic syndrome and are being investigated for use in a number oftumors.[2]
DNA methylation is the modification of DNA nucleotides by addition of a methyl group. These methyl groups are associated with changes in the ability of the corresponding DNA to be used. Patterns of DNA methylation are stable during cellular division. Methylation oftumor suppressor genes in some cancers contributes to the growth and survival of the cancer. Hypomethylating agents decrease the amount of cellular DNA methylation, allowing for tumor suppressor gene expression.[9]
^De Padua Silva L, de Lima M, Kantarjian H, et al. (January 2009). "Feasibility of allo-SCT after hypomethylating therapy with decitabine for myelodysplastic syndrome".Bone Marrow Transplant.43 (11):839–43.doi:10.1038/bmt.2008.400.PMID19151791.
^Garcia-Manero G, Stoltz ML, Ward MR, Kantarjian H, Sharma S (September 2008). "A pilot pharmacokinetic study of oral azacitidine".Leukemia.22 (9):1680–4.doi:10.1038/leu.2008.145.PMID18548103.
^Herman, J. G.; Baylin, S. B. (2003). "Gene silencing in cancer in association with promoter hypermethylation".New England Journal of Medicine.349 (21):2042–54.doi:10.1056/NEJMra023075.PMID14627790.
