The use of hypomethylating agents in the treatment of hematologic malignancies.
Epigenetic alterations, such as DNA methylation and histone modifications, are abnormal in cancer cells, and the use of the hypomethylating agents 5-azacitidine and decitabine are important additions to our arsenal of active cancer drugs, especially for the treatment of the myelodysplastic syndromes and acute myeloid leukemia. Most effective are repeated cycles of the drugs given at doses much lower than originally tested. Typical overall response rates (complete responses + partial responses + hematologic improvement) for both drugs are in the range of 40 - 50%. These agents are generally very well tolerated, with myelosuppression being the major side effect. Postulated to work through hypomethylation of DNA causing induction of gene expression, the precise mechanism of action of these agents is not yet clear. Future studies are likely to combine these agents with other drugs like the histone deacetylase inhibitors that act in related pathways.
Kihslinger
Jane E
JE
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Godley
Lucy A
LA
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019175:DNA Methylation; D000077209:Decitabine; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011788:Quality of Life