Journal
EXPERT OPINION ON DRUG DISCOVERY
Volume 7, Issue 11, Pages 1039-1051Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/17460441.2012.722618
Keywords
acute myeloid leukemia; DNA methyltransferase inhibitors; hypomethylating agents; targeted therapy; treatment
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Introduction: DNA methylation is an epigenetic change mediated by DNA methyltranferases (DNMTs), which are promising epigenetic targets for the treatment of acute myeloid leukemia (AML). This is evidenced by the two DNMT inhibitors (azacitidine and decitabine) approved by the Food and Drug Administration of the United States for the treatment of high-risk myelodysplastic syndromes and the first clinical data available in AML. Areas covered: This paper reviews data from the international literature regarding the design, sites of impact and pharmacodynamic characteristics of DNMT inhibitors, and their first clinical experiences in AML. Expert opinion: The strongest advances in epigenetic therapy have been in the treatment of AML. There are now an increasing number of DNMT inhibitors. These agents may be potentially administered at different times of leukemia therapy: before or instead of chemotherapy, as maintenance therapy, prior to allogeneic stem cell transplant (SCT) or after relapse following SCT.
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