Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
Fels Institute for Cancer Research, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
Nat Rev Genet. 2016 Sep 15;17(10):630-41. doi: 10.1038/nrg.2016.93.
Next-generation sequencing has revealed that more than 50% of human cancers harbour mutations in enzymes that are involved in chromatin organization. Tumour cells not only are activated by genetic and epigenetic alterations, but also routinely use epigenetic processes to ensure their escape from chemotherapy and host immune surveillance. Hence, a growing emphasis of recent drug discovery efforts has been on targeting the epigenome, including DNA methylation and histone modifications, with several new drugs being tested and some already approved by the US Food and Drug Administration (FDA). The future will see the increasing success of combining epigenetic drugs with other therapies. As epigenetic drugs target the epigenome as a whole, these true 'genomic medicines' lessen the need for precision approaches to individualized therapies.
下一代测序技术揭示，超过 50%的人类癌症存在参与染色质组织的酶的突变。肿瘤细胞不仅受到遗传和表观遗传改变的激活，而且还经常利用表观遗传过程来确保它们逃避化疗和宿主免疫监视。因此，最近药物发现工作的重点越来越多地放在针对表观基因组上，包括 DNA 甲基化和组蛋白修饰，有几种新药正在测试中，有些已经被美国食品和药物管理局 (FDA) 批准。未来将看到将表观遗传药物与其他疗法相结合的日益成功。由于表观遗传药物将表观基因组作为一个整体作为靶点，这些真正的“基因组药物”减少了对个体化治疗的精确方法的需求。
