Journal
ANNALS OF HEMATOLOGY
Volume 87, Issue 8, Pages 601-611Publisher
SPRINGER
DOI: 10.1007/s00277-008-0477-9
Keywords
epigenetic treatment; MDS; HDAC inhibitor; DNMT inhibitor; valproic acid; 5-azacytidine; decitabine
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Epigenetic deregulation plays an important role in cancer development. The great interest in epigenetics in hematology and oncology results from the fact that epigenetic, in contrast to genetic, alterations are, in principle, amenable to pharmacological reversal. Epigenetically active drugs currently within clinical trials include histone deacetylase inhibitors (HDACi) and DNA methyltransferase (DNMT) inhibitors. The first treatment approved by the Food and Drug Administration for the treatment of myelodysplastic syndromes (MDS) was the DNMT-inhibitor 5-azacytidine. Currently, two out of three drugs FDA approved for MDS therapy, 5-azacytidine and 5-aza-2'-deoxycytidine, are epigenetically active drugs. Recent clinical trials investigate new dosing schedules, routes of administration, and combination regimens. Several structurally distinct HDACi have been developed. Available data is mostly restricted to phase I trials. The largest experience in MDS and acute myeloid leukemia exists with the anticonvulsant valproic acid. This review summarizes the existing clinical experience on HDACi and DNMT inhibitors. .
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