The Molecular Characterization of Genetic Abnormalities in Esophageal Squamous Cell Carcinoma May Foster the Development of Targeted Therapies

Abstract

Esophageal cancer is among the most common tumors in the world and is associated with poor outcomes, with a 5-year survival rate of about 10–20%. Two main histological subtypes are observed: esophageal squamous cell carcinoma (ESCC), more frequent among Asian populations, and esophageal adenocarcinoma (EAC), the predominant type in Western populations. The development of molecular analysis techniques has led to the definition of the molecular alterations observed in ESCC, consistently differing from those observed in EAC. The genetic alterations observed are complex and heterogeneous and involve gene mutations, gene deletions and gene amplifications. However, despite the consistent progress in the definition of the molecular basis of ESCC, precision oncology for these patients is still virtually absent. The recent identification of molecular subtypes of ESCC with clinical relevance may foster the development of new therapeutic strategies. It is estimated that about 40% of the genetic alterations observed in ESCC are actionable. Furthermore, the recent introduction of solid tumor immunotherapy with immune checkpoint inhibitors (ICIs) showed that a minority of ESCC patients are responsive, and the administration of ICIs, in combination with standard chemotherapy, significantly improves overall survival over chemotherapy in ESCC patients with advanced disease.