Mechanistic insights into the evolution from spasmolytic polypeptide-expressing metaplasia to gastric cancer (Review).

With over 968,000 new cases and approximately 660,000 deaths reported in 2022, gastric cancer represents a global health burden. Despite rising evidence from animal and organoid models identifying spasmolytic polypeptide-expressing metaplasia as a critical precancerous lesion, the mechanisms governing its initiation and progression remain incompletely understood. This review situates spasmolytic polypeptide-expressing metaplasia within the classical Correa cascade and synthesizes current literature by categorizing the underlying mechanisms into six distinct domains: paligenosis, intracellular redox homeostasis, oncogenic pathways, inflammatory responses, parietal cell lineage, and cancer-associated fibroblasts. Furthermore, this article comprehensively summarizes in vivo/vitro and human models of spasmolytic polypeptide-expressing metaplasia, aiming to provide a practical framework for future investigations and, ultimately, to offer novel perspectives on the prevention, diagnosis, and treatment of gastric cancer.