Advances and challenges in gastric cancer testing: the role of biomarkers

Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer. Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment. Human epidermal growth factor receptor 2 (HER2) was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer. Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies, such as pembrolizumab and nivolumab. More recently, zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries. More targeted therapies, including savolitinib for MET-positive patients, are currently under clinical investigation. However, the clinical application of these diagnostic approaches could be hampered by many existing challenges, including invasive and costly sampling methods, variability in immunohistochemistry interpretation, high costs and long turnaround times for next-generation sequencing, the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers, and tumor heterogeneity. Novel testing and analysis techniques, such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry, and emerging therapeutic strategies, including combination therapies that integrate immune checkpoint inhibitors with targeted therapies, offer potential solutions to some of these challenges. This article reviews recent progress in gastric cancer testing, outlines current challenges, and explores future directions for biomarker testing and targeted therapy for gastric cancer.