Extracellular vesicles as regulators of chemotherapy resistance in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) continues to present formidable therapeutic challenges, with treatment outcomes compromised by elevated recurrence frequencies and diminished survival trajectories. Although contemporary multimodal therapeutic protocols have demonstrated progressive refinement, the emergence of pharmaceutical resistance constitutes a predominant barrier to successful clinical intervention. Recent investigations have illuminated the pivotal function of small extracellular vesicle (sEV) populations, with particular emphasis on exosomal populations, as critical mediators orchestrating intercellular dialogue within neoplastic microenvironments. These membrane-enclosed nanostructures have garnered substantial recognition for their integral participation in resistance mechanisms against cytotoxic therapies. The present comprehensive review systematically consolidates contemporary knowledge regarding EV-orchestrated pathways that facilitate chemoresistance in OSCC. The mechanistic landscape examined encompasses the horizontal transfer of regulatory microRNAs, active pharmaceutical extrusion processes, vesicular pH homeostatic perturbations, engagement of survival-promoting signaling networks, modulation of genomic damage repair machinery, immune system reprogramming, epithelial-mesenchymal transitional plasticity, and preservation of stem-like cancer cell populations. Through synthesis of current research advances, this manuscript endeavors to clarify the diverse functional dimensions of EVs in OSCC chemoresistance while establishing a conceptual foundation for future EV-directed therapeutic innovations.