Braun Christian J, Hemann Michael T
a The David H. Koch Institute for Integrative Cancer Research , Cambridge , MA , USA.
b Departments of Biology , Massachusetts Institute of Technology , Cambridge , MA , USA.
Expert Rev Anticancer Ther. 2016 Sep;16(9):977-87. doi: 10.1080/14737140.2016.1212663. Epub 2016 Aug 5.
Whereas tumorigenic processes have traditionally been attributed to gene amplification, deletion, or mutation, it is now clear that epigenetic changes represent an additional hallmark of cancer. This review explains the basic principles of epigenetic regulation and therapy, provides an overview of clinically approved drugs, introduces novel targets and compounds, and discusses the potential reasons behind treatment success and failure.
We provide a brief introduction to the concept of epigenetic regulation in general and explain how epigenetic pathways are altered in cancer. Based on this, we go on to explore the rational behind epigenetic cancer therapy, provide an overview of clinical success and failure of specific drugs, describe novel pharmaceutical targets, review epigenetic combination treatment, and finally discuss biological concepts influencing treatment success. Expert commentary: Even though many early epigenetic therapy trials had disappointing results, lessons learned from these studies have heavily influenced the design of modern trials leading to improved therapeutic outcomes. Better preclinical model systems may help to reduce the risk of clinical failure and to identify high-confidence targets for clinical follow-up.
传统上，致瘤过程被归因于基因扩增、缺失或突变，而现在很清楚，表观遗传变化是癌症的另一个标志。本综述解释了表观遗传调控和治疗的基本原理，概述了临床批准的药物，介绍了新的靶点和化合物，并讨论了治疗成功与失败背后的潜在原因。
我们总体上简要介绍表观遗传调控的概念，并解释癌症中表观遗传途径是如何改变的。在此基础上，我们继续探讨表观遗传癌症治疗背后的原理，概述特定药物的临床成败，描述新的药物靶点，回顾表观遗传联合治疗，最后讨论影响治疗成功的生物学概念。专家评论：尽管许多早期表观遗传治疗试验结果令人失望，但从这些研究中吸取的经验教训对现代试验的设计产生了重大影响，从而改善了治疗效果。更好的临床前模型系统可能有助于降低临床失败的风险，并为临床随访确定高可信度的靶点。
