Epigenetic modifiers: basic understanding and clinical development.
Epigenetic modifiers: basic understanding and clinical development.
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DOI：
10.1158/1078-0432.ccr-08-2788
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Bates SE
中科院分区：
文献类型：
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作者：
Piekarz RL;Bates SE
在细胞培养中首次描述分化和5-氮杂胞苷合成40多年后的60多年里，表观遗传疗法已被添加到抗癌的装备中。DNA甲基转移酶（DNMT）抑制剂如5-aza-2 ' -脱氧胞苷或5-氮杂胞苷已被批准用于骨髓增生异常综合征（MDS）和急性髓性白血病（AML），而组蛋白去乙酰化酶抑制剂（hdi）包括vorinostat、罗米地辛、panobinostat、belinostat和entinostat已被证明在皮肤和周围t细胞淋巴瘤中有活性。尽管迄今为止DNMT抑制剂或hdi单药治疗有效的恶性肿瘤范围有限，但随着联合研究的完成，仍有可能确定更广泛的活性范围。与此同时，基础科学已经为表观基因组的复杂性提供了稳步增长的理解，包括组蛋白代码和异常甲基化的触发器，以及它们对肿瘤发生的贡献。随着我们对癌症表观遗传学的基本了解的增加，潜在治疗靶点的数量也将增加，这为通过使表观基因组正常化来治疗癌症的探索提供了更多的希望。本期CCR焦点致力于理解表观遗传学研究的临床和转化方面。
More than 60 years after the first description of differentiation in cell culture and 40 years after the synthesis of 5-azacytidine,epigenetic therapies have been added to the anticancer armamentarium. DNA methyltransferase (DNMT) inhibitors such as 5-aza-2’-deoxycytidine or 5-azacytidine have been approved in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), whereas the histone deacetylase inhibitors (HDIs) including vorinostat, romidepsin, panobinostat, belinostat, and entinostat have been shown to be active in cutaneous and peripheral T-cell lymphoma. Although the range of malignancies in which monotherapy with DNMT inhibitors or HDIs are effective has been limited to date, the possibility remains that a broader spectrum of activity will be identified as combination studies are completed. Meanwhile, basic science has provided a steadily increasing understanding of the complexity of the epigenome, including the histone code and triggers for aberrant methylation, and their contribution to oncogenesis. As our basic understanding of the epigenetics of cancer increases, the number of potential therapeutic targets will also increase, offering more hope in the quest to treat cancer by normalizing the epigenome. This issue of CCR Focus is dedicated to understanding the clinical and translational aspects of epigenetics research.