Hypomethylating agent

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A hypomethylating agent (or demethylating agent[1]) is a drug that inhibits DNA methylation. Currently available hypomethylating agents block the activity of DNA methyltransferase (DNA methyltransferase inhibitors / DNMT inhibitors). Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, hypomethylating agents are considered a type of epigenetic therapy. Currently two members of the class, azacitidine and decitabine are FDA-approved for use in the United States in myelodysplastic syndrome and are being investigated for use in a number of tumors.[2]

Clinical use[edit]

Two hypomethylating agents are approved for the treatment of myelodysplastic syndrome by the United States FDA[3][4]

Mechanism of action[edit]

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. Excessive methylation of tumor suppressor genes in some cancers contributes to the growth and survival of the cancer. Hypomethylating agents decrease the amount of cellular DNA methylation and disrupt these patterns.[8]

See also[edit]


  1. ^ Garcia-Manero G (November 2008). "Demethylating agents in myeloid malignancies". Curr Opin Oncol 20 (6): 705–10. doi:10.1097/CCO.0b013e328313699c. PMC 3873866. PMID 18841054. 
  2. ^ Hambach L, Ling KW, Pool J, et al. (December 2008). "Hypomethylating drugs convert HA-1 negative solid tumors into targets for stem cell based immunotherapy". Blood 113 (12): 2715–22. doi:10.1182/blood-2008-05-158956. PMID 19096014. 
  3. ^ "Azacitadine - National Cancer Institute". NCI. September 17, 2014. 
  4. ^ "Decitabine - National Cancer Institute". NCI. May 19, 2011. 
  5. ^ Aribi A, Borthakur G, Ravandi F, et al. (February 2007). "Activity of decitabine, a hypomethylating agent, in chronic myelomonocytic leukemia". Cancer 109 (4): 713–7. doi:10.1002/cncr.22457. PMID 17219444. 
  6. ^ 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. PMID 19151791. 
  7. ^ 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. PMID 18548103. 
  8. ^ PMID 14627790 (PubMed)
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