Yan Wenji, Herman James G, Guo Mingzhou
Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China.
The Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 2.18/Research, Pittsburgh, PA 15213, USA.
Epigenomics. 2016 Jan;8(1):119-33. doi: 10.2217/epi.15.84. Epub 2015 Sep 7.
Cancer genome sequencing has created an opportunity for precision medicine. Thus far, genetic alterations can only be used to guide treatment for small subsets of certain cancer types with these key alterations. Similar to mutations, epigenetic events are equally suitable for personalized medicine. DNA methylation alterations have been used to identify tumor-specific drug responsive markers. Methylation of MGMT sensitizes gliomas to alkylating agents is an example of epigenetic personalized medicine. Recent studies have revealed that 5-azacytidine and decitabine show activity in myelodysplasia, lung and other cancers. There are currently at least 20 kinds of histone deacetylase inhibitors in clinical testing. Inhibitors targeting other epigenetic regulators are being clinically tested, such as EZH2 inhibitor EPZ-6438.
癌症基因组测序为精准医学创造了契机。到目前为止,基因改变仅能用于指导某些具有这些关键改变的癌症类型的小部分患者的治疗。与突变类似,表观遗传事件同样适用于个性化医疗。DNA甲基化改变已被用于识别肿瘤特异性药物反应标志物。MGMT甲基化使胶质瘤对烷化剂敏感就是表观遗传个性化医疗的一个例子。最近的研究表明,5-氮杂胞苷和地西他滨在骨髓增生异常综合征、肺癌及其他癌症中显示出活性。目前至少有20种组蛋白脱乙酰酶抑制剂正在进行临床试验。针对其他表观遗传调节因子的抑制剂也正在进行临床试验,如EZH2抑制剂EPZ-6438。