Bridging Pathogens: Epstein-Barr Virus and Helicobacter pylori in Gastric Cancer Stem Cell Regulation

Gastric cancer remains the primary cause of cancer-related deaths worldwide, where gastric cancer stem cells play an essential role in tumor growth and resistance to various gastric cancer therapies. Emerging evidence suggests that the interaction between Epstein-Barr virus and Helicobacter pylori may affect the regulation of gastric cancer stem cells, although the exact mechanism remains to be explored. This mini-review aims to explore the potential interaction between Epstein-Barr virus and Helicobacter pylori in modifying the characteristics of gastric cancer stem cells, emphasizing their respective roles in the inflammatory tumor microenvironment and the synergistic effects on gastric carcinogenesis. This review article presents the impact of Epstein-Barr virus-induced immune evasion and Helicobacter pylori-induced gastric inflammation on the maintenance and differentiation of gastric cancer stem cells. We seek alterations in numerous signaling pathways related to stemness induced by microbial factors. Based on current understanding, several crucial signaling pathways, including the Notch, Hippo pathway, Nuclear factor-κB, wingless-related integration site, and autophagy pathways, have been found to be implicated in Epstein-Barr virus- and Helicobacter pylori-induced gastric cancer stem cells. Understanding this interplay may reveal novel treatment targets for gastric cancer, particularly in patients with chronic infection by these two pathogens. Further research is needed to clarify the mechanistic interactions driving the synergy between Epstein-Barr virus and Helicobacter pylori, which alters the biology of gastric cancer stem cells. This may provide further insights into early diagnosis and treatment approaches for gastric cancer.