Kalebic Thea
Expert Opin Ther Targets. 2003 Dec;7(6):693-9. doi: 10.1517/14728222.7.6.693.
Therapeutic approaches aimed at developing epigenetically-effective drugs are under intense investigation. Several classes of enzymes regulating histone acetylation and DNA methylation, which are required for epigenetic transitions, offer attractive targets for therapeutic interventions. Imbalances in histone acetylation and DNA methylation may play a significant role in the development of cancer and leukaemia and may provide a mechanistic rationale for targeting epigenetic modifications. Clinical trials designed to evaluate inhibitors of DNA methylation and histone deacetylase inhibitors are showing encouraging results in cancer patients. A growing quantity of data from preclinical research supports the notion that epigenetically-effective drugs could also find an application in other therapeutic areas. A number of emerging biomarkers may prove useful for monitoring drug effects and defining molecular signatures of response, toxicity and effective dose.
旨在研发具有表观遗传效应药物的治疗方法正在深入研究中。几类调节组蛋白乙酰化和DNA甲基化的酶是表观遗传转变所必需的，为治疗干预提供了有吸引力的靶点。组蛋白乙酰化和DNA甲基化的失衡可能在癌症和白血病的发生发展中起重要作用，并可能为靶向表观遗传修饰提供机制依据。旨在评估DNA甲基化抑制剂和组蛋白去乙酰化酶抑制剂的临床试验在癌症患者中显示出令人鼓舞的结果。越来越多来自临床前研究的数据支持这样一种观点，即具有表观遗传效应的药物也可应用于其他治疗领域。一些新兴的生物标志物可能有助于监测药物效果，并确定反应、毒性和有效剂量的分子特征。
