Wang He, DeFina Samuel M, Bajpai Manisha, Yan Qin, Yang Lei, Zhou Zhongren
Department of Pathology, Yale School of Medicine, Yale University New Haven, Connecticut, United States.
Department of Medicine-Gastroenterology and Hepatology, Rutgers-Robert Wood Johnson Medical School, Rutgers The State University of New Jersey New Brunswick, NJ, United States.
Am J Cancer Res. 2021 Nov 15;11(11):5644-5658. eCollection 2021.
Esophageal carcinoma (EC) is one of the most pervasive cancers in the world, with upwards of 500,000 new diagnoses, annually. Despite its prominence, advancements in the detection and treatment of EC have been marginal over the past 30 years and the survival rate continues to stay below 20%. This is due to the uncommonly heterogeneous presentation of EC which presents unprecedented challenges in improving patient survival and quality of care. However, distinct epigenetic alterations to the DNA methylome may provide an avenue to drastically improve the detection and treatment of EC. Specifically, the creation of novel biomarker panels that consist of EC-specific methylation markers have shown promise as a potential alternative to the more invasive, contemporary diagnostic methods. Additionally, growing insight into the biological and clinical properties of EC-specific methylation patterns have opened a window of opportunity for enhanced treatment; of growing interest is the application of "DNMT inhibitors" - a class of drugs which inhibit excessive methylation and have been shown to re-sensitize chemoresistant tumors. Here we provide a comprehensive review of the current advancements in EC DNA methylation to underscore a potential approach to its detection and treatment.
食管癌(EC)是世界上最常见的癌症之一,每年有超过50万例新诊断病例。尽管其发病率很高,但在过去30年里,食管癌的检测和治疗进展甚微,生存率仍低于20%。这是由于食管癌表现出异常的异质性,给提高患者生存率和护理质量带来了前所未有的挑战。然而,DNA甲基化组的独特表观遗传改变可能为大幅改善食管癌的检测和治疗提供一条途径。具体而言,由食管癌特异性甲基化标记组成的新型生物标志物面板已显示出有望成为更具侵入性的当代诊断方法的潜在替代方案。此外,对食管癌特异性甲基化模式的生物学和临床特性的深入了解为强化治疗打开了一扇机会之窗;越来越受关注的是“DNA甲基转移酶抑制剂”的应用——这一类药物可抑制过度甲基化,并已被证明能使化疗耐药肿瘤重新敏感。在此,我们对食管癌DNA甲基化的当前进展进行全面综述,以强调其检测和治疗的潜在方法。