Etiology, Therapeutic Challenges, Drug Interactions, and Future Directions of Gastric Ulcer Progression to Gastric Cancer

Vollständiger Abstract

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Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, and chronic gastric ulceration represents an important precursor lesion in a subset of patients. This narrative review aimed to synthesize evidence published between 2015 and 2026 on the etiology and pathogenesis of gastric ulcer, current therapeutic strategies, the preclinical roles of laboratory animals, treatment failures, and the transition from gastric ulcer to gastric cancer. The progression from chronic inflammation to malignancy is driven by a complex interplay of bacterial virulence factors, host responses, and molecular alterations. Laboratory animal models have provided important preclinical evidence for evaluating gastric mucosal injury, histopathological changes, diagnostic biomarkers, and carcinogenic progression. In particular, rodent and mouse models have supported the development of molecular and fluorescence-based imaging approaches for detecting ulcerative, dysplastic, and malignant gastric lesions. Helicobacter pylori (H. pylori) infection and prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary etiological factors in the development of gastric ulcer, while host susceptibility, environmental influences, and microbial interactions further contribute to disease progression. Recent advances have improved understanding of the molecular mechanisms underlying gastric mucosal injury, ulcer healing, and carcinogenesis, including CagA-mediated signaling, the spermine oxidase (SMOX) pathway, and microbiota-derived metabolites. Despite the widespread use of proton pump inhibitors and H. pylori eradication diets, increasing antibiotic resistance and refractory ulcers continue to limit treatment success. Emerging biomarkers, innovative acid-suppressive agents, microbiome-based strategies, and advanced imaging technologies present promising strategies for improving diagnosis and treatment. Integrating findings from experimental animal models with clinical evidence could improve diagnostic timing, risk prediction, and the development of targeted strategies to prevent the progression of gastric ulcers to gastric cancer.