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DNA甲基化对药物作用的影响日渐受到关注。许多编码药物代谢酶、药物转运体、核受体及药物靶点的基因受DNA甲基化调控。DNA甲基化在影响细胞色素P450酶(CYP450)的表达水平上起着重要的作用,而CYP450酶系催化多种药物代谢反应,能显著影响药物疗效。目前的研究也发现DNA甲基化水平在个体间的差异与药物疗效和不良反应在个体间的差异是紧密相关的。DNA甲基化状态会受药物作用影响,进而引起不同程度的药物不良反应。近年来,以DNA甲基化为靶向的药物研发呈增长态势,DNA甲基转移酶抑制剂对肿瘤等重大疾病治疗具决定性作用。临床试验结果显示,DNA甲基化药物治疗已在改善药物疗效、稳定药理作用及减少药物不良反应上初见成效。DNA甲基化可能成为早期预测药物效应的潜在生物标记,将成为实现临床个体化用药的有力工具。
The impact of DNA methylation on the role of drugs has drawn increasing attention. Many genes encoding drug-metabolizing enzymes, drug transporters, nuclear receptors and drug targets are regulated by DNA methylation. DNA methylation plays an important role in affecting the expression of cytochrome P450 enzymes (CYP450), while CYP450 enzyme catalyzes a variety of drug metabolism reactions, which can significantly affect drug efficacy. The current study also found that differences in DNA methylation levels between individuals and drug efficacy and adverse reactions in the inter-individual differences are closely related. DNA methylation status will be affected by the drug effect, which in turn cause different degrees of adverse drug reactions. In recent years, DNA methylation-targeted drug development showed an increasing trend, and DNA methyltransferase inhibitors play a decisive role in the treatment of major diseases such as tumors. Clinical trial results showed that DNA methylation drug treatment has achieved initial success in improving drug efficacy, stabilizing pharmacological effects and reducing adverse drug reactions. DNA methylation may be a potential biomarker for early prediction of drug effects and will be a powerful tool for clinical individualized use.