Kronfol Mohamad M, Dozmorov Mikhail G, Huang Rong, Slattum Patricia W, McClay Joseph L
Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, USA.
Department of Biostatistics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Expert Rev Precis Med Drug Dev. 2017;2(1):33-45. doi: 10.1080/23808993.2017.1284557. Epub 2017 Jan 31.
Epigenetics is the study of reversible modifications to chromatin and their extensive and profound effects on gene regulation. To date, the role of epigenetics in personalized medicine has been under-explored. Therefore, this review aims to highlight the vast potential that epigenetics holds.
We first review the cell-specific nature of epigenetic states and how these can vary with developmental stage and in response to environmental factors. We then summarize epigenetic biomarkers of disease, with a focus on diagnostic tests, followed by a detailed description of current and pipeline drugs with epigenetic modes of action. Finally, we discuss epigenetic biomarkers of drug response.
Epigenetic variation can yield information on cellular states and developmental histories in ways that genotype information cannot. Furthermore, in contrast to fixed genome sequence, epigenetic patterns are plastic, so correcting aberrant, disease-causing epigenetic marks holds considerable therapeutic promise. While just six epigenetic drugs are currently approved for use in the United States, a larger number is being developed. However, a drawback to current therapeutics is their non-specific effects. Development of locus-specific epigenetic modifiers, used in conjunction with epigenetic biomarkers of response, will enable truly precision interventions.
表观遗传学是对染色质可逆修饰及其对基因调控的广泛而深远影响的研究。迄今为止,表观遗传学在个性化医疗中的作用尚未得到充分探索。因此,本综述旨在突出表观遗传学所具有的巨大潜力。
我们首先回顾表观遗传状态的细胞特异性本质,以及这些状态如何随发育阶段变化并对环境因素作出反应。然后,我们总结疾病的表观遗传生物标志物,重点关注诊断测试,接着详细描述具有表观遗传作用模式的现有及在研药物。最后,我们讨论药物反应的表观遗传生物标志物。
表观遗传变异能够以基因型信息无法做到的方式产生有关细胞状态和发育历史的信息。此外,与固定的基因组序列不同,表观遗传模式具有可塑性,因此纠正异常的致病表观遗传标记具有相当大的治疗前景。虽然目前在美国仅有六种表观遗传药物获批使用,但正在研发更多药物。然而,当前疗法的一个缺点是它们具有非特异性效应。开发位点特异性表观遗传修饰剂,并与反应的表观遗传生物标志物联合使用,将实现真正的精准干预。