Cancer Biology and Epigenomics Program, Ann & Robert H Lurie Children's Hospital of Chicago Research Center and Department of Pediatrics, Northwestern University's Feinberg School of Medicine, 225 E. Chicago Avenue, Box 220, Chicago, IL 60611-2605, USA.
Cancer Biology and Epigenomics Program, Ann & Robert H Lurie Children's Hospital of Chicago Research Center and Department of Pediatrics, Northwestern University's Feinberg School of Medicine, 225 E. Chicago Avenue, Box 220, Chicago, IL 60611-2605, USA; StartUp Health Academy, 2000 Broadway St, 18th Floor, New York, NY 10.023, USA; Genomic Enterprise, 2405 N. Sheffield Av., # 14088, Chicago, IL 60.614, USA; Genomic Sciences and Biotechnology Program, UCB - Brasilia, SGAN 916 Modulo B, Bloco C, 70.790-160 Brasilia, Brazil.
Pharmacol Ther. 2015 Jul;151:72-86. doi: 10.1016/j.pharmthera.2015.03.003. Epub 2015 Mar 20.
Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting.
表观遗传学是一种分子现象，涉及基因表达的可遗传变化，而不涉及 DNA 序列的变化。整个基因组的表观遗传修饰，即表观基因组，在正常发育和疾病中的基因表达调控中起着至关重要的作用。传统的表观遗传变化包括 DNA 甲基化和组蛋白修饰。最近的证据表明，其他因素，如非编码 RNA，可能具有表观遗传调节作用。异常的表观遗传信号正在成为人类疾病的一个核心组成部分，而表观遗传修饰的可逆性为开发临床相关治疗方法提供了一个令人兴奋的机会。目前的表观遗传学治疗方法通过破坏 DNA 甲基转移酶或组蛋白去乙酰化酶提供临床益处。然而，下一代表观遗传学治疗方法的出现为更有效地破坏表观遗传疾病状态提供了机会。新型表观遗传学治疗方法可能改善药物靶向和药物递送，优化给药方案，并提高现有治疗方式（化疗、放疗和免疫疗法）的疗效。本文讨论了导致疾病的表观遗传机制、现有的表观遗传学治疗方法、目前正在开发的表观遗传学治疗方法，以及表观遗传学治疗在临床环境中的潜在未来应用。
