CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
FEBS J. 2022 Mar;289(5):1276-1301. doi: 10.1111/febs.15966. Epub 2021 Jun 25.
The molecular characterization of mechanisms underlying transcriptional control and epigenetic inheritance since the 1990s has paved the way for the development of targeted therapies that modulate these pathways. In the past two decades, cancer genome sequencing approaches have uncovered a plethora of mutations in chromatin modifying enzymes across tumor types, and systematic genetic screens have identified many of these proteins as specific vulnerabilities in certain cancers. Now is the time when many of these basic and translational efforts start to bear fruit and more and more chromatin-targeting drugs are entering the clinic. At the same time, novel pharmacological approaches harbor the potential to modulate chromatin in unprecedented fashion, thus generating entirely novel opportunities. Here, we review the current status of chromatin targets in oncology and describe a vision for the epigenome-modulating drugs of the future.
自 20 世纪 90 年代以来，对转录控制和表观遗传遗传机制的分子特征的研究为靶向治疗的发展铺平了道路，这些靶向治疗可以调节这些途径。在过去的二十年中，癌症基因组测序方法已经揭示了肿瘤类型中大量染色质修饰酶的突变，系统的遗传筛选已经确定了许多这些蛋白质是某些癌症的特定弱点。现在，许多这些基础和转化努力开始取得成果，越来越多的靶向染色质的药物正在进入临床。与此同时，新的药理学方法有可能以前所未有的方式调节染色质，从而产生全新的机会。在这里，我们回顾了肿瘤学中染色质靶点的现状，并描述了未来表观基因组修饰药物的前景。
