Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Onco Targets Ther. 2013;6:223-32. doi: 10.2147/OTT.S34680. Epub 2013 Mar 21.
The emergence of epigenetic mechanisms as key regulators of gene expression has led to dramatic advances in understanding cancer biology. Driven by complex layers that include aberrant DNA methylation and histone modification, epigenetic aberrations have emerged as critical processes that disrupt cellular machinery and homeostasis. Recent discoveries have already translated into successful clinical trials and improved patient care, with several agents approved for hematologic disease and others undergoing study. As the field matures, substantial challenges persist that will require resolution. These include the need to decipher more fully the interplay between the epigenetic and genetic machinery, patient selection and improving treatment efficacy in solid tumors, and optimizing combination therapies to counteract chemoresistance and minimize adverse effects. Here, we review recent progress in epigenetic treatments and consider their implications for future cancer therapy.
表观遗传机制作为基因表达的关键调节剂的出现,使得人们对癌症生物学的理解取得了巨大进展。受包括异常 DNA 甲基化和组蛋白修饰在内的复杂层驱动,表观遗传异常已成为破坏细胞机制和动态平衡的关键过程。最近的发现已经转化为成功的临床试验和改善的患者护理,已有几种药物获批用于血液疾病,其他药物正在研究中。随着该领域的成熟,仍存在需要解决的重大挑战。这些挑战包括需要更全面地阐明表观遗传和遗传机制之间的相互作用、患者选择以及提高实体瘤治疗效果,以及优化联合治疗以对抗化疗耐药性并最小化不良反应。在这里,我们回顾了表观遗传治疗的最新进展,并考虑了它们对未来癌症治疗的影响。