Spasmolytic polypeptide-expressing metaplasia in the progression of gastric precancerous lesions: mechanisms and therapeutic opportunities—a narrative review
Year: 2026
Type: review
Abstract: Background and Objective: Spasmolytic polypeptide-expressing metaplasia (SPEM) represents a gastric metaplastic phenotype situated at the intersection of mucosal repair and preneoplastic remodeling. While transient SPEM may facilitate epithelial restitution following acute injury, persistent SPEM in chronic inflammatory contexts correlates with incomplete intestinal metaplasia (IM), dysplastic epithelial states, and gastric carcinogenesis. This narrative review summarizes the biological characteristics and proposed cellular origins of SPEM. It critically examines the mechanisms governing SPEM initiation, persistence, and progression-associated remodeling. It also evaluates the evidence linking SPEM to incomplete IM and gastric carcinogenesis and discusses emerging therapeutic vulnerabilities and their translational limitations. Methods: PubMed and Web of Science were searched for English-language studies published from January 1, 2000 to April 30, 2026. Reference lists of relevant studies and guidelines were also screened. Human, animal, organoid, and other experimental studies with direct mechanistic or clinical relevance were included. Key Content and Findings: eradication remains the only recognized upstream intervention; SPEM-directed strategies remain preclinical. Conclusions: SPEM is a context-dependent reparative lineage whose association with preneoplastic remodeling is strongest in chronic injury. Human evidence links persistent SPEM to incomplete IM and dysplasia-associated states but does not establish an obligatory SPEM-to-IM-to-cancer sequence. Future progress requires distinguishing transient reparative SPEM from persistent, progression-associated SPEM, standardizing phenotypic criteria, conducting longitudinal human studies, and identifying targets that suppress pathological SPEM without impairing mucosal repair.
Source: Translational Cancer Research
Authors: Xiangye Zhang, Keyan Shi, Jian Gao
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223871843