Unlocking the Potential: Epstein-Barr Virus (EBV) in Gastric Cancer and Future Treatment Prospects, a Literature Review

Abstract

Gastric cancer (GC) is a complex disease with various etiologies. While Helicobacter pylori infection is still one of the leading risk factors for GC, increasing evidence suggests a link between GC and other infective agents such as Epstein Bar Virus (EBV). EBV-associated gastric cancer (EBVaGC) is now recognized as a distinct subgroup of GC, and the complex interactions between the virus and gastric mucosa may influence its development. A recent integrative analysis of the genome and proteome of GC tissues by The Cancer Genome Atlas project has identified EBVaGC as a specific subtype characterized by PIK3CA and ARID1A mutations, extensive DNA hyper-methylation, and activation of immune signaling pathways. These molecular characteristics are markers of the unique molecular profile of this subset of GC and are potential targets for therapy. This review aims to provide an overview of the current knowledge on EBVaGC. It will focus on the epidemiology, clinic-pathological features, and genetic characteristics of EBVaGC. Additionally, it will discuss recent data indicating the potential use of EBV infection as a predictive biomarker of response to chemotherapy and immune checkpoint inhibitors. The review also delves into potential therapeutic approaches for EBVaGC, including targeted therapies and adoptive immunotherapy, highlighting the promising potential of EBV as a therapeutic target.

Keywords: biomarker; epstein-barr virus; gastric cancer; molecular classification; treatment options.

Figure 1

(a) EBV-associated gastric carcinoma exhibiting a typical lymphoepithelioma-like carcinoma morphology; (b) Tumor cells of an EBV-associated lymphoepithelioma-like carcinoma showing strong EBER reactivity (EBER in-situ hybridization).