Conventional and Novel Approaches to Establishing Mouse Models of Gastric Cancer in the Past, Present, and Potential Post-H. Pylori Infection Era

Gastric cancer remains a major cause of global cancer-related morbidity and mortality. Mouse models are indispensable tools for preclinical research into its mechanisms and therapies. Although Helicobacter pylori (H. pylori) infection is the primary risk factor for gastric cancer, developing mouse models based on this pathogen faces significant challenges. These include low bacterial colonization and survival rates, unpredictable and protracted tumorigenesis timelines, restrictions of host genetic backgrounds, the complexity of inflammatory and immune microenvironments, difficulties in standardized pathological assessment, and poor model reproducibility. In light of these limitations, research efforts have diversified into four principal categories of modeling approaches: chemical carcinogen-induced models, microbe-infected models (particularly those involving H. pylori), xenograft models, and genetically engineered mouse models. Each strategy offers distinct advantages and constraints, necessitating careful selection based on specific research objectives. This review comprehensively examines both conventional and emerging methods for establishing gastric cancer mouse models, situating them within a historical and evolving research landscape from past reliance on H. pylori to present and future approaches in the potential post-H. pylori infection era. We emphasize the applicability and compatibility of each modeling system with particular research goals, providing critical insights for selecting optimal in vivo platforms to advance the study of gastric carcinogenesis.