title: Current status of epigenetic treatment in myelodysplastic syndromes.
abstract: 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.
authors.affiliation: Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine University, Düsseldorf, Germany. kuendgen@med.uni-duesseldorf.de
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuendgen
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D000077209:Decitabine; D001374:Azacitidine