Epigenetics in Esophageal Cancer: From Mechanisms to Therapeutics

Esophageal cancer is a leading cause of cancer-related deaths worldwide. In the past few years, the roles of epigenetics in cancer have been fully accepted. Recently, there has been an increased focus on epigenetic alterations underlying esophageal cancer carcinogenesis, with several epigenetic drug and RNA interference therapies being tested. However, the conclusion that epigenetic alterations are linked directly to an increased or decreased risk of esophageal cancer is less certain. Therefore, there is an urgent need to test novel epigenetic biomarkers for diagnostic and prognostic significance and to explore their potential as therapeutic targets. In this review, the discussion is concentrated on epigenetic alterations involving super-enhancers, DNA methylation, histone modifications, and multiple noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and their impact on tumor growth, invasion, metastasis, and drug resistance. Then specific instances of using epigenetic drugs, such as DNA methyltransferase and histone deacetylase inhibitors, to treat esophageal cancer are described. Recent developments in miRNA-based therapeutic strategies, including antagomirs, lock nucleic acids, miRNA sponges, and microRNA replacement therapies, against esophageal cancer are also highlighted.