Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy.
Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy.
复制标题
DOI：
--
复制
发表时间：
2015-02
影响因子：
2
通讯作者：
Philip Lee;Ben Murphy;Rickey Miller;Vivek D. Menon;N. Banik;P. Giglio;S. Lindhorst;A. Varma;W. Vandergrift;Sunil J. Patel;Arabinda Das
中科院分区：
文献类型：
--
作者：
Philip Lee;Ben Murphy;Rickey Miller;Vivek D. Menon;N. Banik;P. Giglio;S. Lindhorst;A. Varma;W. Vandergrift;Sunil J. Patel;Arabinda Das
胶质母细胞瘤是成人中最常见和最致命的恶性原发性脑肿瘤（IV级星形细胞瘤）。目前的标准治疗方法已经有所改善，但患者预后仍然是不可接受的破坏性。胶质母细胞瘤复发与表观遗传机制和细胞途径有关。因此，更多地了解胶质母细胞瘤的细胞、遗传和表观遗传起源是推进胶质母细胞瘤治疗的关键。一个快速发展的治疗领域，表观遗传修饰剂;组蛋白脱乙酰酶抑制剂（HDACis），现在已经显示出通过调节组蛋白的乙酰化状态（表观遗传调节的一种形式）和其他非组蛋白靶点来改善患者预后的很大希望。HDAC抑制剂已在临床前环境中显示为经由多种机制的有效抗癌剂，通过上调肿瘤抑制基因的表达、抑制癌基因、抑制肿瘤血管生成和上调免疫系统。目前有许多HDAC抑制剂处于各种类型癌症的临床前和临床研究阶段。这篇综述将解释表观遗传学癌症治疗的理论，确定HDAC抑制剂，正在研究胶质母细胞瘤治疗，解释临床前和临床研究所证明的治疗效果的机制，并描述这些药物的发展现状，因为它们属于胶质母细胞瘤治疗。
Glioblastoma is the most common and deadliest of malignant primary brain tumors (Grade IV astrocytoma) in adults. Current standard treatments have been improving but patient prognosis still remains unacceptably devastating. Glioblastoma recurrence is linked to epigenetic mechanisms and cellular pathways. Thus, greater knowledge of the cellular, genetic and epigenetic origin of glioblastoma is the key for advancing glioblastoma treatment. One rapidly growing field of treatment, epigenetic modifiers; histone deacetylase inhibitors (HDACis), has now shown much promise for improving patient outcomes through regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other non-histone protein targets. HDAC inhibitors have been shown, in a pre-clinical setting, to be effective anticancer agents via multiple mechanisms, by up-regulating expression of tumor suppressor genes, inhibiting oncogenes, inhibiting tumor angiogenesis and up-regulating the immune system. There are many HDAC inhibitors that are currently in pre-clinical and clinical stages of investigation for various types of cancers. This review will explain the theory of epigenetic cancer therapy, identify HDAC inhibitors that are being investigated for glioblastoma therapy, explain the mechanisms of therapeutic effects as demonstrated by pre-clinical and clinical studies and describe the current status of development of these drugs as they pertain to glioblastoma therapy.