Emerging Genomic Biomarkers in Metastatic Gastric Cancer: Prognostic and Therapeutic Implications

Abstract

Background: Gastric cancer (GC) represents the fourth most prevalent malignancy globally and the second leading cause of cancer-related mortality. The anatomical location of gastric tumors significantly influences their pathological characteristics, with gastric antrum cancers typically manifesting as intestinal-type carcinomas associated with Helicobacter pyloriinfection, whereas fundus and cardia lesions more commonly exhibit diffuse-type histology.

Recent Advances: The integration of conventional tumor markers, including CEA and CA19-9, has demonstrated significant diagnostic utility. CA19-9 exhibits 56% sensitivity and 74% specificity for detecting recurrence, with sensitivity increasing to 87% when combined with CEA [3,4]. Molecular profiling has identified actionable genomic alterations, including HER2 amplification (15-20%), MSI-H (3-5%), and emerging targets such as CLDN18.2 (30-40%) and FGFR2b (5-10%).

Clinical Implications: The VIKTORY umbrella trial demonstrated that tumor genomic profiling can effectively guide targeted treatment selection in metastatic gastric cancer, establishing a paradigm for precision oncology. HER2-targeted therapy with trastuzumab, immune checkpoint inhibitors, and emerging agents targeting novel molecular pathways have transformed the therapeutic landscape.

Conclusion: The incorporation of genomic biomarkers into clinical practice enables personalized treatment approaches, improving patient selection and therapeutic outcomes in metastatic gastric cancer. Future directions include the integration of liquid biopsy technologies and comprehensive genomic profiling to advance precision oncology.