Animal models and pathogenesis of gastric cancer: from premalignant conditions-to-metastasis

Gastric cancer (GC) remains one of the most prevalent malignancies of the gastrointestinal tract worldwide, ranking fifth in incidence and continuing to be a leading cause of cancer-related mortality. Elucidating the mechanisms underlying GC development and progression, as well as exploring effective preventive and therapeutic strategies, is therefore of paramount importance. Animal models are indispensable tools in this endeavor, providing platforms to investigate carcinogenic processes, recapitulate disease features, and evaluate therapeutic interventions, thereby bridging the gap between laboratory discoveries and clinical application. However, the establishment of reliable GC models remains challenging due to variations in tumor induction techniques, experimental conditions, and the profound heterogeneity and aggressive metastatic potential of GC. In this review we systematically summarize animal models used for studying gastric premalignant conditions and GC organized by disease stage. We analyze recent advances and limitations of each model, considering methodologic approaches, underlying mechanisms, and translational potential. Particular emphasis is placed on aligning model characteristics with contemporary clinical challenges. Ultimately, we highlight the pivotal role of animal models in advancing precision medicine for GC, offering novel perspectives to inform both mechanistic research and therapeutic development.