Ellis Leigh, Pili Roberto
Roswell Park Cancer Institute, Genitourinary Program, Grace Cancer Drug Center, Buffalo, NY 14263, USA;
Pharmaceuticals (Basel). 2010 Aug 1;3(8):2411-2469. doi: 10.3390/ph3082441.
Advancement in the understanding of cancer development in recent years has identified epigenetic abnormalities as a common factor in both tumorigenesis and refractory disease. One such event is the dysregulation of histone deacetylases (HDACs) in both hematological and solid tumors, and has consequently resulted in the development of HDAC inhibitors (HDACI) to overcome this. HDACI exhibit pleiotropic biological effects including inhibition of angiogenesis and the induction of autophagy and apoptosis. Although HDACI exhibit modest results as single agents in preclinical and clinical data, they often fall short, and therefore HDACI are most promising in combinational strategies with either standard treatments or with other experimental chemotherapies and targeted therapies. This review will discuss the induction of autophagy and apoptosis and the inhibition of angiogenesis by HDACI, and also pre-clinical and clinical combination strategies using these agents.
近年来，对癌症发展的认识取得了进展，已确定表观遗传异常是肿瘤发生和难治性疾病的共同因素。其中一个事件是血液系统肿瘤和实体瘤中组蛋白脱乙酰酶（HDACs）的失调，因此开发了HDAC抑制剂（HDACI）来克服这一问题。HDACI具有多效性生物学效应，包括抑制血管生成以及诱导自噬和凋亡。尽管HDACI在临床前和临床数据中作为单一药物显示出一定效果，但往往不尽人意，因此HDACI在与标准治疗或其他实验性化疗及靶向治疗的联合策略中最具前景。本综述将讨论HDACI诱导自噬和凋亡以及抑制血管生成的作用，以及使用这些药物的临床前和临床联合策略。
