Institute of Experimental & Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.
Epigenomics. 2012 Aug;4(4):369-81. doi: 10.2217/epi.12.39.
Chemoresistance of tumors is often reported to be due to overexpression of efflux transporters or genetic alterations of signaling pathways. More recently, there is increasing evidence that epigenetic modification contributes to the phenomenon of drug resistance. Despite alteration of DNA methylation or histone modifications, deregulated miRNA expression patterns of tumor cells have been identified as interfering with drug response. Attempts to modify the expression of selected miRNAs have partly led to intriguing improvements of chemotherapy response. This review focuses on the major epigenetic mechanisms, including the role of miRNA expression contributing to drug resistance and the role of epigenetic drugs to overcome nonresponse arising under conventional chemotherapy.
肿瘤的化学抗性通常归因于外排转运体的过度表达或信号通路的遗传改变。最近越来越多的证据表明，表观遗传修饰有助于耐药现象的发生。尽管 DNA 甲基化或组蛋白修饰发生了改变，但肿瘤细胞中 miRNA 表达模式的失调已被确定为干扰药物反应的因素。试图修饰选定 miRNA 的表达已在一定程度上导致化疗反应的显著改善。这篇综述主要关注主要的表观遗传机制，包括 miRNA 表达在耐药中的作用以及表观遗传药物在克服常规化疗中出现的无反应中的作用。
