Gastric organoids: A promising model for studying "inflammation-cancer" transition in atrophic gastritis

Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer, while gastric organoid technology, especially region-specific modeling, provides a more precise in vitro platform for studying this carcinogenic mechanism. Helicobacter pylori activates carcinogenic signaling pathways through virulence factors, inducing DNA damage, epigenetic dysregulation, and immune microenvironment imbalance, driving inflammation-cancer conversion. Intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia serve as critical precursor lesions, gradually developing into dysplasia and adenocarcinoma under the influence of chronic inflammation and genetic instability through intestinal cell transformation and high trefoil factor 2-expressing cell expansion. The immune suppression, metabolic reprogramming, and matrix remodeling within the tumor microenvironment collaboratively create a pro-cancer ecosystem that accelerates inflammation-carcinogenesis transformation. The gastric organoid model successfully simulates the spatiotemporal dynamics of the carcinogenesis process in atrophic gastritis, and its future integration with single-cell omics, real-time imaging technologies, and artificial intelligence technologies could provide a more precise platform for elucidating molecular mechanisms and screening intervention strategies. These advances position gastric organoids as pivotal tools for clinical translation, enabling personalized risk stratification, early intervention targeting precancerous transitions, and ex vivo prediction of patient-specific therapeutic responses to guide precision management of gastric cancer.