Marks Paul A, Dokmanovic Milos
Memorial Sloan-Kettering Cancer Center, Cell Biology Program, Sloan-Kettering Institute for Cancer Research, New York City, New York 10021, USA.
Expert Opin Investig Drugs. 2005 Dec;14(12):1497-511. doi: 10.1517/13543784.14.12.1497.
Histone deacetylase (HDAC) inhibitors are a new class of targeted anticancer agents. Several HDAC inhibitors are in clinical trials and have shown significant activity against a spectrum of both haematological and solid tumours at doses that are well tolerated by patients. HDACs and histone acetyltransferases can, by reversible acetylation, modify the structure and function of histones and proteins in transcription factor complexes, which are involved in the regulation of gene expression, as well as many non-histone proteins that are involved in regulating cell proliferation and cell death. HDAC inhibitors are a structurally diverse group of molecules; these agents selectively alter the expression of genes. HDAC inhibitors can induce cancer cell death, whereas normal cells are relatively resistant to HDAC inhibitor-induced cell death.
组蛋白去乙酰化酶（HDAC）抑制剂是一类新型的靶向抗癌药物。几种HDAC抑制剂正在进行临床试验，并且已显示出在患者耐受性良好的剂量下对一系列血液系统肿瘤和实体瘤具有显著活性。HDAC和组蛋白乙酰转移酶可通过可逆的乙酰化作用，修饰参与基因表达调控的转录因子复合物中的组蛋白和蛋白质的结构与功能，以及许多参与调节细胞增殖和细胞死亡的非组蛋白。HDAC抑制剂是一类结构多样的分子；这些药物可选择性地改变基因表达。HDAC抑制剂可诱导癌细胞死亡，而正常细胞对HDAC抑制剂诱导的细胞死亡相对耐药。
