Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies.
Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies.
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DOI：
10.3390/ph3082441
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发表时间：
2010-08-01
期刊：
影响因子：
--
通讯作者：
Pili R
中科院分区：
文献类型：
--
作者：
Ellis L;Pili R
近年来对癌症发展的理解的进步已经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学和实体肿瘤中组蛋白去乙酰化酶（HDAC）的失调，因此导致HDAC抑制剂（HDACI）的发展来克服这一问题。HDACI具有多种生物学作用，包括抑制血管生成和诱导自噬和细胞凋亡。尽管在临床前和临床数据中，HDACI作为单一药物表现出适度的效果，但它们经常达不到预期，因此HDACI在与标准治疗或其他实验性化疗和靶向治疗的联合策略中最有希望。本文就HDACI诱导细胞自噬、细胞凋亡、抑制血管生成的作用及其临床前和临床联合应用策略作一综述。
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.