DNA methyltransferase inhibitors in acute myeloid leukemia: discovery, design and first therapeutic experiences

被引：20

作者：

Thomas, Xavier ^{[1
,2
]}

机构：

[1] Ctr Hosp Lyon Sud, Serv Hematol Clin, Hospices Civils Lyon, F-69495 Pierre Benite, France

[2] Claude Bernard Lyon I Univ, INSERM, U590, Lyon, France

来源：

EXPERT OPINION ON DRUG DISCOVERY | 2012年 / 7卷 / 11期

关键词：

acute myeloid leukemia; DNA methyltransferase inhibitors; hypomethylating agents; targeted therapy; treatment; RISK MYELODYSPLASTIC SYNDROME; CONVENTIONAL CARE REGIMENS; DNMT3A MUTATIONS; ELDERLY-PATIENTS; INTENSIVE CHEMOTHERAPY; HYPOMETHYLATING AGENT; PROGNOSTIC-FACTOR; SILENCED GENES; OLDER PATIENTS; VALPROIC ACID;

D O I：

10.1517/17460441.2012.722618

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：1039 / 1051

页数：13

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