Mehnert Janice M, Kelly Wm Kevin
Department of Medical Oncology, Yale Cancer Center, New Haven, CT 06520-8032, USA.
Cancer J. 2007 Jan-Feb;13(1):23-9. doi: 10.1097/PPO.0b013e31803c72ba.
Histone deacetylases (HDACs) and histone acetyltransferases are enzymes that regulate chromatin structure and function through the removal and addition, respectively, of the acetyl group from the lysine residues of core nucleosomal histones. This posttranslational modification of histones is an important process in the regulation of gene expression. Aberrant expression and recruitment and disrupted activities of HDACs and histone acetyltransferases have been found in malignant tissues, implicating their involvement in cancer. HDAC inhibitors (HDACIs) function through diverse mechanisms, including the promotion of cell cycle arrest and apoptosis and the inhibition of angiogenesis. Malignant cells appear more sensitive to the proapoptotic effects of HDACIs, underscoring the therapeutic potential of these agents. Multiple HDACIs are currently under investigation in clinical trials, including vorinostat (suberoylanilide hydroxamic acid), which was recently approved by the U.S. Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients with progressive, persistent, or recurrent disease on or after 2 systemic therapies.
组蛋白去乙酰化酶（HDACs）和组蛋白乙酰转移酶是分别通过从核心核小体组蛋白的赖氨酸残基上去除和添加乙酰基来调节染色质结构和功能的酶。这种组蛋白的翻译后修饰是基因表达调控中的一个重要过程。在恶性组织中发现HDACs和组蛋白乙酰转移酶的异常表达、募集及活性紊乱，提示它们与癌症有关。HDAC抑制剂（HDACIs）通过多种机制发挥作用，包括促进细胞周期停滞和凋亡以及抑制血管生成。恶性细胞似乎对HDACIs的促凋亡作用更敏感，这突出了这些药物的治疗潜力。目前多种HDACIs正在进行临床试验研究，包括伏立诺他（辛二酰苯胺异羟肟酸），它最近被美国食品药品监督管理局批准用于治疗接受过2次全身治疗后病情进展、持续或复发的皮肤T细胞淋巴瘤患者的皮肤表现。
