Therapeutic opportunities in EBV-positive gastric cancer subtypes

Journal article : Review

Immunotherapy has shown inconsistent results in Epstein–Barr virus-associated gastric cancer (EBVaGC) despite being associated with an active tumour microenvironment. This calls for the identification of subtypes within the EBVaGC subtype, and subsequent treatments tailored for their properties. This review identified six different EBVaGC subtypes alongside potential therapeutic opportunities. EBVaGCs, which express immune checkpoints, high microsatellite instability or high tumour mutational burden, are shown to respond better to immune checkpoint inhibitors, each due to their own specific characteristics. Co-infection of EBV and Helicobacter pylori in gastric cancer (GC) can exacerbate their impact on inflammatory stress and has the potential to be treated by antiviral agents and antimicrobials. EBVaGCs are also more likely to express wild-type p53 than other GCs, which suggests potential for lytic-induction therapy, where the EBV genome is kicked out of latency and subsequently killed using antiviral nucleoside analogue prodrugs. Lastly, EBVaGC is more likely to express the PI3K and ARID1A mutations, which can potentially be treated using PI3K/mTOR dual inhibitors and Akt/PARP inhibitors. These six subtypes could aid the selection of more successful treatments for EBVaGC, thereby improving the current overall survival and prognosis of patients.

Authors: Al-Sattar, H; Owen, R; Jaafari, AM; Saha, A; Ayyappan, K

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: SAGE Publications
• Journal: Therapeutic Advances in Medical Oncology
• Volume: 17
• Article number: 17588359251396619
• Publication date: 2025-12-03
• Acceptance date: 2025-10-27
• DOI: 10.1177/17588359251396619
• EISSN: 1758-8359
• ISSN: 1758-8340
• Language: English
• Keywords: EBV; gastric cancer; Epstein–Barr virus; immune biomarkers; EBV-positive gastric cancer; immunotherapy
• Subtype: Review