[Research progress on the treatment and drug resistance of microsatellite instability-high gastric cancer].

Mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) gastric cancer represents a distinct molecular subtype of gastric cancer. Although immunotherapy has significantly improved survival outcomes in patients with this subtype, its overall efficacy remains limited by primary and acquired resistance. This review provides a comprehensive overview of recent research progress in dMMR/MSI-H gastric cancer,aiming to provide a reference for individualized and precision therapy. (1) It elucidates the molecular definition of dMMR/MSI-H and summarizes the principles, advantages, clinical applications, and limitations of current detection methodologies. (2) It outlines the clinicopathological and molecular biological characteristics of this subtype, emphasizing its unique immunological features. (3) The review examines the evolution and optimization of therapeutic strategies-from conventional chemotherapy to immune checkpoint inhibitor monotherapy and combination immunotherapy-supported by relevant clinical evidence. (4) It further summarizes the underlying mechanisms of immunotherapy resistance, integrates recent studies and emerging strategies to overcome resistance, discusses the ongoing exploration and prospects of organ-preserving treatment strategies, and outlines future research directions.