Molecular Biology and Clinical Management of Esophageal Adenocarcinoma

Abstract

Esophageal adenocarcinoma (EAC) is a highly lethal malignancy. Due to its rising incidence, EAC has become a severe health challenge in Western countries. Current treatment strategies are mainly chosen based on disease stage and clinical features, whereas the biological background is hardly considered. In this study, we performed a comprehensive review of existing studies and discussed how etiology, genetics and epigenetic characteristics, together with the tumor microenvironment, contribute to the malignant behavior and dismal prognosis of EAC. During the development of EAC, several intestinal-type proteins and signaling cascades are induced. The anti-inflammatory and immunosuppressive microenvironment is associated with poor survival. The accumulation of somatic mutations at the early phase and chromosomal structural rearrangements at relatively later time points contribute to the dynamic and heterogeneous genetic landscape of EAC. EAC is also characterized by frequent DNA methylation and dysregulation of microRNAs. We summarize the findings of dysregulations of specific cytokines, chemokines and immune cells in the tumor microenvironment and conclude that DNA methylation and microRNAs vary with each different phase of BE, LGD, HGD, early EAC and invasive EAC. Furthermore, we discuss the suitability of the currently employed therapies in the clinic and possible new therapies in the future. The development of targeted and immune therapies has been hampered by the heterogeneous genetic characteristics of EAC. In view of this, the up-to-date knowledge revealed by this work is absolutely important for future EAC studies and the discovery of new therapeutics.

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

“…For EGA, biomarker assessment, including HER2, PD-L1, and mismatch repair status, guides treatment decisions. Trastuzumab is recommended for HER2-overexpressing EAC, while ICIs show efficacy in HER2-negative adenocarcinomas with high or intermediate PD-L1 expression or deficient mismatch repair [ 98 ]. EACs are further stratified based on HER2 expression, PD-L1 status, and mismatch repair status, influencing the choice between chemotherapy alone, chemotherapy plus immunotherapy, or targeted therapies [ 98 ].…”

“…Trastuzumab is recommended for HER2-overexpressing EAC, while ICIs show efficacy in HER2-negative adenocarcinomas with high or intermediate PD-L1 expression or deficient mismatch repair [ 98 ]. EACs are further stratified based on HER2 expression, PD-L1 status, and mismatch repair status, influencing the choice between chemotherapy alone, chemotherapy plus immunotherapy, or targeted therapies [ 98 ]. In the case of ESCC, chemotherapy combined with immunotherapy is preferred, showcasing greater activity compared to chemotherapy alone, particularly in patients with higher PD-L1 expression [ 72 , 99 ].…”

Stratification of Barrett’s esophagus surveillance based on p53 immunohistochemistry: a cost-effectiveness analysis by an international collaborative group

“…Barrett's esophagus (BE) is a precursor lesion to esophageal adenocarcinoma (EAC) [1]. The prognosis of patients developing EAC remains dismal, with 5-year survival still only ~20% [2,3,4]. The efficacy of endoscopic surveillance of BE to detect dysplasia at a population level appears to be modest, but most guidelines do suggest surveillance, which is widely practiced [5,6,7,8,9].…”