Exosomal signaling in esophageal cancer: mechanisms, detection, and therapeutic innovations.

Abstract

Esophageal cancer is increasingly understood as a malignancy shaped not only by local histopathologic change but also by dynamic intercellular communication within the tumor ecosystem. Exosomes and related small extracellular vesicles are secreted by tumor, stromal, endothelial, and immune cells and carry nucleic acids, proteins, lipids, and metabolites that may contribute to tumor growth, invasion, immune escape, metastatic niche formation, and treatment resistance. Their molecular cargo may capture tumor-associated biological changes before overt radiologic or histopathologic progression in selected settings; however, their clinical utility remains constrained by inconsistent isolation methods, heterogeneous cargo profiles, limited prospective validation, and insufficient standardization. This review critically synthesizes current evidence on exosome-mediated communication in esophageal cancer, with emphasis on mechanistic signaling, liquid biopsy, treatment monitoring, and engineered therapeutic delivery. Current data suggest that exosome-associated miRNAs, lncRNAs, circRNAs, proteins, and immune-regulatory molecules are promising candidate biomarkers, but they should currently be regarded as complementary rather than superior to endoscopy, imaging, ctDNA, circulating tumor cells, and clinicopathologic assessment. Engineered exosomes show preclinical promise as delivery vehicles for nucleic acids, immunomodulators, and chemotherapeutics, although their clinical translation in esophageal cancer remains limited by manufacturing reproducibility, biodistribution, safety, dose control, and regulatory requirements. Overall, exosome-based strategies may become part of precision oncology for esophageal cancer only if supported by standardized extracellular-vesicle methodology, prospective multicenter validation, and evidence that exosome-informed decisions improve patient outcomes. CORE TIPS: Emerging evidence suggests that exosomes participate in multiple stages of esophageal cancer biology, including local invasion, immune modulation, lymphatic dissemination, treatment resistance, and candidate biomarker development. Their molecular cargo may provide dynamic biological information before conventional clinical progression becomes apparent in selected studies, but their screening and monitoring value requires prospective head-to-head validation against endoscopy, imaging, ctDNA, circulating tumor cells, and tissue-based biomarkers. Engineered exosomes represent a promising preclinical delivery platform; however, clinical translation depends on standardized isolation and characterization, cargo normalization, batch-to-batch reproducibility, scalable production, and regulatory-quality control. This review therefore emphasizes both translational opportunities and current evidence limitations.