Promising New Platforms and Targets in the Management of Gastroesophageal Cancers

Gastric and gastroesophageal junction cancers remain a major global cause of cancer-related mortality. Despite incremental advances in surgery and systemic therapy, durable survival gains have been limited, underscoring persistent unmet medical needs. However, the treatment paradigm has undergone a rapid transformation, driven by the integration of immunotherapy in curative-intent systemic treatment and the expansion of biomarker-guided systemic therapies. In the perioperative setting, immune checkpoint inhibitors combined with optimized cytotoxic chemotherapy have demonstrated encouraging efficacy, with recent phase III trials contributing to the establishment of combination of immunotherapy and chemotherapy as an emerging therapeutic platform. In advanced disease, precision oncology frameworks continue to expand beyond traditional biomarkers. Established targets such as human epidermal growth factor receptor 2 are now complemented by newly validated markers including claudin18.2, whereas additional actionable alterations-such as MET and TROP2-are actively under clinical investigation. These developments are redefining treatment algorithms and introducing new sequencing considerations, particularly in the context of tumor heterogeneity and biomarker coexpression. Concurrent advances in molecular diagnostics and next-generation sequencing are also facilitating the comprehensive identification of therapeutically relevant alterations. This review outlines the evolving therapeutic landscape of gastric and gastroesophageal junction cancers, spanning perioperative immunotherapy, newly validated molecular targets, and next-generation drug development platforms. By integrating biomarker-driven strategies with innovative modalities, such as antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor-T-cell therapy, and vaccines, we highlight how precision therapeutics are reshaping treatment paradigms across resectable and advanced disease.