Ahuja Nita, Sharma Anup R, Baylin Stephen B
Cancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; email:
Annu Rev Med. 2016;67:73-89. doi: 10.1146/annurev-med-111314-035900.
The past 15 years have seen an explosion of discoveries related to the cellular regulation of phenotypes through epigenetic mechanisms. This regulation provides a software that packages DNA, without changing the primary base sequence, to establish heritable patterns of gene expression. In cancer, many aspects of the epigenome, controlled by DNA methylation, chromatin, and nucleosome positioning, are altered as one means by which tumor cells maintain abnormal states of self-renewal at the expense of normal maturation. Epigenetic and genetic abnormalities thus collaborate in cancer initiation and progression, as exemplified by frequent mutations in genes encoding proteins that control the epigenome. There is growing emphasis on using epigenetic therapies to reprogram neoplastic cells toward a normal state. Many agents targeting epigenetic regulation are under development and entering clinical trials. This review highlights the promise that epigenetic therapy, often in combination with other therapies, will become a potent tool for cancer management over the next decade.
在过去的15年里，通过表观遗传机制对细胞表型调控的相关发现呈爆发式增长。这种调控提供了一种软件，在不改变DNA基本碱基序列的情况下对其进行包装，以建立可遗传的基因表达模式。在癌症中，由DNA甲基化、染色质和核小体定位控制的表观基因组的许多方面都会发生改变，这是肿瘤细胞以牺牲正常成熟为代价维持自我更新异常状态的一种方式。表观遗传和遗传异常因此在癌症的发生和发展中相互协作，例如编码控制表观基因组蛋白质的基因频繁发生突变。人们越来越重视使用表观遗传疗法使肿瘤细胞重新编程恢复正常状态。许多针对表观遗传调控的药物正在研发并进入临床试验阶段。这篇综述强调了表观遗传疗法（通常与其他疗法联合使用）在未来十年将成为癌症治疗有力工具的前景。
