Comprehensive modeling of the Correa cascade in precancerous lesions of gastric cancer: Leveraging animal, cellular, and organoid systems for translational insights

BACKGROUND Precancerous lesions of gastric cancer (PLGC), including chronic atrophic gastritis, intestinal metaplasia, and dysplasia, constitute key transitional stages in the Correa cascade toward gastric cancer. Understanding these stages is essential for early detection, prevention, and therapeutic intervention. AIM To provide a comprehensive and critical overview of current animal, cellular, and organoid models used in PLGC research, emphasizing their applications, translational relevance, and emerging technologies. METHODS A scoping systematic review was performed according to the PRISMA-ScR framework. Literature was identified from PubMed and Web of Science up to June 2025 using predefined keywords and Boolean operators. Eligible studies included experimental reports describing animal, cellular, or organoid models of PLGC. Two authors independently screened titles, abstracts, and full texts, and relevant data were charted and synthesized narratively. RESULTS This study delineates the modeling strategies for PLGC across various platforms. Animal models, including chemical induction with N-methyl-N’-nitro-N-nitrosoguanidine, N-nitroso-N-methylurea, Helicobacter pylori infection, transgenic approaches, and composite modeling, recapitulate the histopathological spectrum of PLGC and facilitate mechanistic discovery. Cellular models simulate chronic inflammation and carcinogen exposure, enabling high-throughput mechanistic screening. Gastric organoids derived from patients or animals offer a physiologically relevant three-dimensional culture system, reproducing epithelial transformation and Helicobacter pylori -induced pathology, with recent advances in co-culture systems and immune-organoid interactions. Integration of gene editing, single-cell transcriptomics, and organoid-on-chip platforms is expected to further refine PLGC modeling and accelerate clinical translation. CONCLUSION Integrated PLGC models provide a robust framework for elucidating the cellular and molecular basis of early gastric tumorigenesis. Their continued evolution will enhance biomarker discovery, immunologic investigation, and therapeutic development.