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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Tong Ye,
  • Mingyang Ma,
  • Wenjing Sun,
  • Mengran Zhao,
  • Peng Li

摘要

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.