Gastric cancer remains a significant global health challenge, demanding innovative therapeutic approaches to combat tumor resistance mechanisms. The Epithelial Cell Adhesion Molecule (EpCAM) has emerged as a potential target for Chimeric Antigen Receptor (CAR) T cell therapy. However, the efficacy of this promising treatment is hampered by tumor resistance mechanisms. This article comprehensively reviews the current understanding of tumor resistance mechanisms in gastric cancer, with a specific focus on EpCAM-targeted CAR T cell therapy. From genetic alterations to microenvironmental factors, we explore the intricate landscape of resistance mechanisms and discuss strategies to overcome these challenges for improving the clinical success of CAR T cell therapy in gastric cancer.
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