Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Cell Biology and Genetics Program, 1275 York Ave, New York, NY 10065, USA.
Expert Opin Investig Drugs. 2010 Sep;19(9):1049-66. doi: 10.1517/13543784.2010.510514.
Histone deacetylase (HDAC) inhibitors are being developed as a new, targeted class of anticancer drugs.
This review focuses on the mechanisms of action of the HDAC inhibitors, which selectively induce cancer cell death.
There are 11 zinc-dependent HDACs in humans and the biological roles of these lysine deacetylases are not completely understood. It is clear that these different HDACs are not redundant in their activity. This review focuses on the mechanisms by which HDAC inhibitors can induce transformed cell growth arrest and cell death, inhibit cell mobility and have antiangiogenesis activity. There are more than a dozen HDAC inhibitors, including hydroxamates, cyclic peptides, benzamides and fatty acids, in various stages of clinical trials and many more compounds in preclinical development. The chemically different HDAC inhibitors may target different HDACs.
There are extensive preclinical studies with transformed cells in culture and tumor-bearing animal models, as well as limited clinical studies reported to date, which indicate that HDAC inhibitors will be most useful when used in combination with cytotoxic or other targeted anticancer agents.
组蛋白去乙酰化酶（HDAC）抑制剂正在被开发为一种新的、靶向的抗癌药物。
这篇综述集中于 HDAC 抑制剂的作用机制，它选择性地诱导癌细胞死亡。
人类中有 11 种锌依赖性 HDAC，这些赖氨酸去乙酰化酶的生物学作用尚不完全清楚。很明显，这些不同的 HDAC 在其活性中并不是多余的。这篇综述集中于 HDAC 抑制剂如何诱导转化细胞生长停滞和细胞死亡、抑制细胞迁移以及具有抗血管生成活性的机制。目前有十几种 HDAC 抑制剂，包括羟肟酸、环肽、苯甲酰胺和脂肪酸，处于不同的临床试验阶段，还有更多的化合物处于临床前开发阶段。化学结构不同的 HDAC 抑制剂可能针对不同的 HDAC。
目前已有大量关于转化细胞培养和荷瘤动物模型的临床前研究，以及有限的临床研究报告，这些研究表明，HDAC 抑制剂在与细胞毒性或其他靶向抗癌药物联合使用时将最有用。
