Marks Paul A, Miller Thomas, Richon Victoria M
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Curr Opin Pharmacol. 2003 Aug;3(4):344-51. doi: 10.1016/s1471-4892(03)00084-5.
Post-translational modification of the histones of chromatin has a fundamental role in regulating gene expression. Enzymes involved in these epigenetic events include histone deacetylases (class I and class II), which can be inhibited by a structurally diverse group of small molecules. These histone deacetylase inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. Results of clinical trials with several of these agents have indicated that they are well tolerated at doses that have anti-tumour activity.
染色质组蛋白的翻译后修饰在调节基因表达中起基本作用。参与这些表观遗传事件的酶包括组蛋白脱乙酰酶(I类和II类),它们可被一组结构多样的小分子抑制。这些组蛋白脱乙酰酶抑制剂在体外和体内均可诱导癌细胞生长停滞、分化和/或凋亡。几种此类药物的临床试验结果表明,在具有抗肿瘤活性的剂量下,它们具有良好的耐受性。