Cancer development in esophageal epithelium

Abstract

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are aggressive forms of cancer affecting the esophageal epithelium. These cancers are associated with a poor prognosis and a 5-year survival rate of approximately 25%. The epithelial cells lining the esophagus have built-in defense mechanisms against cancer, known as epithelial defense against cancer (EDAC). One mechanism involves clonal competition within the esophageal epithelium. Normal cells with Notch1 mutations compete with other mutated cells, restricting the clonal expansion of mutant clones. However, ESCC and EAC tumors persist, suggesting that cancer cells find ways to evade these natural safeguard mechanisms. Recent research suggests that cell competition also plays a role in tumor initiation. Furthermore, there seems to be a critical role for the interaction with the tumor microenvironment in supporting tumor development. This review aims to explore the latest discoveries in esophageal cancer development, shedding light on the molecular mechanisms that enable tumor cells to evade the suppression mechanisms and establish cancerous growth. Understanding these mechanisms will contribute to uncovering new therapeutic interventions and improve outcomes for ESCC and EAC patients.