Papait Roberto, Monti Elena, Bonapace Ian M
University of Insubria, Department of Structural and Functional Biology, Via A da Giussano, 12 Busto Arsizio, I-21052, Italy.
Curr Opin Drug Discov Devel. 2009 Mar;12(2):264-75.
Epigenetic changes occurring during the development of organisms can be altered by the presence of synthetic substances in the environment, resulting in developmental reprogramming and disease. The occurrence of such changes supports the theory that diseases might be cured by altering the epigenetic regulation of gene expression, either directly by modifying the control of the misregulated genes that cause a disease, or indirectly by 'reprogramming' cells toward a 'normal' gene expression pattern. Launched drugs that inhibit DNA methyltransferases or histone deacetylases and lead to epigenetic changes are currently in use for the treatment of cancer. In addition, recent advancements in the understanding of epigenetic mechanisms involved in tumor development and neurodisorders have enabled new approaches for the development of specific epigenetic therapies.
生物体发育过程中发生的表观遗传变化可因环境中合成物质的存在而改变,从而导致发育重编程和疾病。此类变化的发生支持了这样一种理论,即疾病或许可以通过改变基因表达的表观遗传调控来治愈,要么直接通过改变导致疾病的失调基因的控制,要么间接通过将细胞“重编程”为“正常”的基因表达模式。目前已上市的抑制DNA甲基转移酶或组蛋白脱乙酰酶并导致表观遗传变化的药物正用于癌症治疗。此外,对肿瘤发生和神经疾病所涉及的表观遗传机制的最新认识进展,为开发特定的表观遗传疗法带来了新方法。