Cancer treatment of the future: Inhibitors of histone methyltransferases
Cancer treatment of the future: Inhibitors of histone methyltransferases
复制标题
DOI：
10.1016/j.biocel.2008.07.024
复制
发表时间：
2009-01-01
影响因子：
4
通讯作者：
Jung, Manfred
中科院分区：
文献类型：
--
作者：
Spannhoff, Astrid;Sippl, Wolfgang;Jung, Manfred
人类的癌症是一个多步骤过程的结果。这个过程通常包括致癌基因的激活和/或肿瘤抑制基因的失活。这两个步骤不仅是由突变引起的，也可能是易位或转录速率改变的结果。一个重要的机制是表观遗传改变的发生，如启动子甲基化（可能导致肿瘤抑制因子沉默）或组蛋白乙酰化降低（可能导致肿瘤抑制因子沉默）或参与细胞凋亡的蛋白质。今天，组蛋白乙酰化和DNA甲基化是与人类癌症病理密切相关的表观遗传修饰，临床使用的两类酶抑制剂近在咫尺。相比之下，表观遗传学的其他领域仍然缺乏类似的全面知识。对于组蛋白甲基转移酶及其抑制剂组尤其如此。因为历史甲基化模式和癌症进展之间的联系已经被认识到。组蛋白甲基转移酶是未来癌症治疗的有希望的靶点。(C) 2008 Elsevier Ltd版权所有。
Cancer in humans is the result of a multi-step process. This process often involves the activation of oncogenes and/or the inactivation Of tumor suppressor genes. These two steps arise not only due to mutations, but Call also be the result of a translocation or an altered transcription rate. One important mechanism is the occurrence of epigenetic alterations like promotor methylation (which may lead to tumor suppressor silencing) or decreased histone acetylation (which may lead to tumor suppressor silencing) or proteins involved in apoptosis). Today, histone acetylation and DNA methylation are epigenetic modifications which have been linked closely to the pathology of human cancers and inhibitors of both enzyme classes for clinical use are at hand. In contrast,other fields of epigenetics still lack of similarly thorough knowledge. This is especially true for the group of histone methyltransferases and their inhibitors. Since connections between historic methylation patterns and cancer progression have been recognized. histone methyltransferases represent promising targets for future cancer treatment. (C) 2008 Elsevier Ltd. All rights reserved.