Histone deacetylase inhibitor and demethylating agent chromatin compaction and the radiation response by cancer cells
Histone deacetylase inhibitor and demethylating agent chromatin compaction and the radiation response by cancer cells
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DOI：
10.1097/ppo.0b013e31803c7565
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发表时间：
2007-01-01
期刊：
影响因子：
2.2
通讯作者：
Gius, David
中科院分区：
文献类型：
--
作者：
Bar-Sela, Gil;Jacobs, Kristi Muldoon;Gius, David
现在看来，表观遗传学在体外和体内的转化中都发挥着核心作用。DNA甲基化的表达和调控以及随后的染色质结构在肿瘤细胞中发生了显著的变化，提示在体内细胞转化过程中发挥了直接作用。如果表观遗传学和历史的翻译后修饰在转化中起作用，那么调控染色质压缩的基因也可能是描述肿瘤细胞耐药性的分子靶标和标记似乎是合乎逻辑的。染色质的局部重塑是基因表达调控的关键步骤，改变这些基因的表达也可能有利于改变肿瘤细胞对抗癌药物的反应。几种改变染色质紧凑的新药物，甲基转移酶或组蛋白去乙酰酶抑制剂，正在进行临床试验，并在与放射相结合时显示出良好的临床前相互作用。在这篇综述中，我们讨论了组蛋白脱乙酰酶抑制剂作为放射增敏剂的潜力。
It now appears that epigenetics plays a central role in transformation, both in vitro and in vivo. The expression and regulation of DNA methylation and the subsequent chromatin structure are significantly altered in tumor cells, suggesting a direct role in the process of in vivo cellular transformation. If epigenetics and posttranslational modifications of histories play a role in transformation, then it seems logical that the genes regulating chromatin compaction may also be molecular targets and markers in profiling tumor cell resistance. Local remodeling of chromatin is a key step in the regulation of gene expression, and altering the expression of these genes might also favorably alter how tumor cells respond to anticancer agents. Several new agents that alter chromatin compaction, either methyltransferase or histone deacetylases inhibitors, are progressing through clinical trials and have shown promising preclinical interactions when combined with radiation. In this review, we discuss the potential for histone deacetylases inhibitors as radio-sensitizing agents.