Antibody-Mediated Therapy in Gastric Cancer: Past, Present, and Future

Gastric cancer has historically relied on cytotoxic chemotherapy, yet its considerable mo lecular heterogeneity has limited therapeutic efficacy. The development of anti-body-mediated therapies has marked a new era in precision oncology, enabling selective targeting of biomarkers such as HER2, VEGFR2, PD-1/PD-L1, and CLDN18.2. This review summarizes the evolution of antibody-based strategies in gastric cancer, beginning with trastuzumab, the first HER2-targeted treatment, followed by the decade-long stagnation after the failure of T-DM1, and the recent establishment of trastuzumab deruxtecan (T-DXd) as a new standard of care. We further examine advances in anti-angiogenic therapy with ramucirumab, the incorporation of immune checkpoint inhibitors such as nivolumab and pembrolizumab into first-line regimens, and the clinical validation of CLDN18.2, culmi-nating in the approval of zolbetuximab. Emerging modalities—including next-generation antibody–drug conjugates (ADCs), bispecific antibodies, TROP2-directed agents, and CLDN18.2-targeted CAR-T cells—are also discussed. Finally, key challenges such as treatment resistance, real-time biomarker monitoring, and optimal sequencing in mul-ti-biomarker–positive patients are explored. Collectively, antibody-mediated therapy con-tinues to shift gastric cancer management toward increasingly personalized and durable treatment strategies.