Targeting Epigenetic Aberrations in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer in most of sub-Saharan Africa and Asia, including China. Both genetic and epigenetic aberrations have been considered playing a crucial role in the initiation and progression of ESCC. Although the genetic aberrations in ESCC, including mutations in TP53, CDKN2A, and PIK3CA, have been very well studied, targeted therapies for ESCC are still limited to trastuzumab, ramucirumab, and pembrolizumab according to the National Comprehensive Cancer Network (NCCN) guideline. Studies on the epigenetics of ESCC have exploded over the last two decades. These studies have identified epigenetic aberrations in ESCC, including DNA methylation, histone modification, and non-coding RNA. These epigenetic aberrations are frequently involved in cell development and differentiation through regulating gene expression, suggesting their promising potential in ESCC treatment and chemoprevention. To date, much work remains to complete the epigenomic landscape in ESCC, to connect epigenetic aberrations to genetic aberrations and to use this crosstalk between the genome and the epigenome to guide the development and applications of new targeted therapies for ESCC.