Abstract
Chemotherapy resistance is a major obstacle in gastric cancer, limiting the efficacy of systemic therapy and contributing to poor survival. Tumor-derived exosomes are key mediators of chemoresistance, carrying microRNAs, long noncoding RNAs, and proteins that modulate apoptosis, drug efflux, and tumor-microenvironment interactions. Evidence from high-incidence countries, such as China and Japan, associates specific exosomal signatures with poor treatment response, and translational studies in Europe and North America are exploring their prognostic and predictive utility. Despite technical advances, clinical translation is hampered by inconsistent protocols, small cohorts, and limited regulatory frameworks. This letter reviews the biological and clinical evidence for exosome-mediated chemoresistance in gastric cancer and advocates for standardized methodologies, global validation studies, and integration into precision oncology pathways.