Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.

Gastric cancer (GC) is one of the malignant tumors with high incidence and mortality worldwide. It has concealed early symptoms, poor prognosis for advanced patients, and limited efficacy of conventional treatments. Metabolic reprogramming is a core hallmark of cancer, among which amino acid metabolic reprogramming plays a critical regulatory role in the initiation and progression of GC. By linking intracellular energy supply, biosynthetic demands, and tumor microenvironment remodeling, it participates in immune escape, redox homeostasis maintenance, and therapeutic resistance. Dysregulation of key amino acids, including arginine, tryptophan, glutamine, branched-chain amino acids, serine/glycine, and aspartic acid, as well as altered expression and activity of rate-limiting enzymes and key catalytic enzymes, collectively drive the proliferation, invasion, metastasis, and stemness maintenance of GC cells. These metabolic enzymes can serve as potential biomarkers for the diagnosis and prognosis of GC, and are also important targets for precision therapy. At present, progress has been made in the development of inhibitors targeting key enzymes in amino acid metabolism. Single-target therapy or its combination with chemotherapy and immunotherapy has shown promising application prospects, but challenges such as clinical translation bottlenecks and unclear drug resistance mechanisms still exist. This review systematically summarizes the roles and molecular mechanisms of key amino acid metabolic enzymes in the occurrence and development of GC, and sorts out the research status of related targeted therapies, so as to provide references for basic research and clinical translation of metabolic precision therapy for GC.