Precision oncology in gastric cancer: navigating molecular subtypes, therapeutic targets, and future horizons

Gastric cancer (GC) remains a leading cause of cancer-related mortality globally and is characterized by significant inter- and intra-tumoral heterogeneity, which poses major challenges to effective treatment. Although traditional "one-size-fits-all" chemotherapy regimens have improved outcomes, the prognosis for advanced disease remains poor, necessitating a paradigm shift towards personalized medicine. This review provides a comprehensive synthesis of the current landscape of precision oncology in GC. We systematically analyze the clinical implications of major molecular classification systems, particularly The Cancer Genome Atlas (TCGA) subtypes (EBV-positive, MSI-H, GS, and CIN), and their role in guiding therapeutic stratification. The integration of molecular profiling has revolutionized the management of GC. We discuss the evolution of targeted therapies, ranging from established standards, like HER2 inhibition, to emerging targets, including Claudin18.2 and FGFR2, highlighting their potential of overcoming resistance mechanisms. Furthermore, we evaluate the efficacy of immune checkpoint inhibitors (PD-1/PD-L1 blockade), specifically in the context of high microsatellite instability (MSI-H) and EBV-positive subtypes, where these have demonstrated robust antitumor activity. Beyond tissue-based markers, this article also explores the expanding role of liquid biopsies, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), as non-invasive tools for real-time monitoring of disease progression and therapeutic response. Precision oncology represents a transformative approach in GC, moving beyond histology to a molecularly driven treatment framework. However, realizing its full potential requires addressing challenges related to tumor heterogeneity and drug resistance. Future research must focus on validating novel biomarkers and developing synergistic combination strategies to further improve patient survival.