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

Table 3 Decision framework for selecting precancerous lesions of gastric cancer research models

Research objective	Model	Induction/approach	Advantages	Limitations
SPEM mechanisms	Mouse (acute drug-induced)	DMP-777 (10-14 days), L635 (10-14 days)	Rapid, reversible, specific parietal cell loss	Lacks chronic inflammatory context
IM	Mouse (bile acid-induced), GES-1 cells, gastric organoids	Mouse: 0.2% DCA in drinking water (6 months); GES-1: 100 μM CDCA for 24 hours. Organoids: BMP activation	In vivo: Recapitulates IM progression. In vitro: Rapid, high-throughput. Organoids: Human-specific, physiologically relevant	In vivo: Long duration. In vitro: Lack tissue complexity. Organoids: Lack full tumor microenvironment
H. pylori pathogenesis	Mongolian gerbil, C57BL/6 mouse	H. pylori inoculation (e.g., TN2GF4, 7.13, PMSS1)	Gerbils: Full Correa cascade to adenocarcinoma. Mice: Genetic tools available, suitable for immune studies	Gerbils: Limited genetic tools. Mice: Resistant to many H. pylori strains
Multifactorial carcinogenesis	Composite rat/mouse models	MNNG/MNU + H. pylori; MNNG/MNU + high-salt diet + ranitidine	Models human synergistic etiology; high clinical relevance	Complex setup, multiple variables to control
Genetic and molecular mechanisms	GEMMs (e.g., INS-GAS, p53KO), CRISPR-edited organoids	Genetic manipulation (e.g., KrasG12D, TP53-/-)	Definitive genotype-phenotype studies; precise temporal control	High cost, technical complexity
Drug screening and toxicity	Cell lines (GES-1, BGC823)	Acute or chronic MNNG/MNU treatment or H. pylori co-culture	High-throughput, low cost, reproducible	Simplified system, lacks in vivo physiology
Immune-microenvironment interactions	Immune-organoid co-culture	Co-culture with macrophages (RAW264.7) or PBMCs	Incorporates human immune components; personalized potential	Technically challenging; not fully vascularized

IM: Intestinal metaplasia; H. pylori: Helicobacter pylori; GES-1: Gastric epithelial cell-1; GEMM: Genetically engineered mouse models; INS-GAS: Insulin-gastrin; CDCA: Chenodeoxycholic acid; DCA: Deoxycholic acid; MNU: N-Nitroso-N-methylurea; MNNG: N-methyl-N’-nitro-N-nitrosoguanidine; TP53: Tumor protein 53; PBMCs: Peripheral blood mononuclear cells.