Kihslinger Jane E, Godley Lucy A
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Leuk Lymphoma. 2007 Sep;48(9):1676-95. doi: 10.1080/10428190701493910.
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.
表观遗传改变，如DNA甲基化和组蛋白修饰，在癌细胞中是异常的，而使用5-氮杂胞苷和地西他滨等去甲基化药物是我们活性抗癌药物库中的重要补充，特别是用于治疗骨髓增生异常综合征和急性髓系白血病。最有效的是重复给药周期，给药剂量远低于最初测试的剂量。这两种药物的典型总体缓解率（完全缓解+部分缓解+血液学改善）在40%-50%的范围内。这些药物通常耐受性良好，骨髓抑制是主要副作用。推测这些药物通过DNA去甲基化导致基因表达诱导而起作用，但其确切作用机制尚不清楚。未来的研究可能会将这些药物与其他作用于相关途径的药物如组蛋白去乙酰化酶抑制剂联合使用。
