Therapeutic Frontiers in Gastroesophageal Cancer: Contemporary Concepts in Management and Therapy.

Gastroesophageal cancer (GEC) represents a global health burden, with rising incidence and high mortality. Despite advancements in early detection and systemic therapies, outcomes remain poor, especially in advanced stages. Management requires a multidisciplinary, multimodal approach that integrates surgery, chemotherapy, radiotherapy, targeted agents, and immunotherapy, tailored by tumor histology, location, and molecular profile. For localized disease, perioperative chemotherapy or chemoradiotherapy is standard, with adjuvant immunotherapy now emerging in selected high-risk cases. In metastatic or unresectable settings, systemic therapy forms the backbone of treatment, with biomarker-driven regimens targeting HER2, PD-L1, MSI-H/dMMR, and CLDN18.2, offering improved outcomes. Novel agents and combinations, including bispecific antibodies, FGFR2 inhibitors, and immunotherapy-based strategies, are actively being explored in clinical trials. This review provides a comprehensive overview of the evolving therapeutic landscape of GEC. It emphasizes the growing role of precision medicine and the integration of emerging clinical data into practice.