Extracellular Vesicles as Precision Tools in Cancer: From Molecular Mechanisms to Clinical Applications

Extracellular vesicles (EVs), including exosomes, play a central role in intercellular communication in cancer. They regulate tumour growth, microenvironmental remodelling, immune responses, and therapeutic resistance through the transfer of proteins, lipids, and nucleic acids. The molecular cargo of EVs reflects the biological state of parental tumour cells, positioning EVs as promising tools for investigating cancer progression and therapeutic adaptation. Oncogenic signalling pathways have been reported to influence EV biogenesis, cargo loading, and cellular uptake. MicroRNAs and other non-coding RNAs carried by EVs modulate gene expression and influence tumour behaviour. EV-mediated metabolic reprogramming may contribute to tumour survival and resistance to therapy. These molecular mechanisms highlight the functional diversity of tumour-associated EVs. Advanced experimental platforms have improved the physiological relevance of EV research. Three-dimensional cancer models, including spheroids, organoids, and organ-on-chip systems, have uncovered context-dependent EV functions that are not observed in conventional two-dimensional cultures. Disease-specific EV signatures have been evaluated across major malignancies, including breast, lung, colorectal, prostate, glioblastoma, and haematological cancers. These signatures reflect tumour heterogeneity, metastatic potential, and disease evolution. Tumour-derived EVs demonstrate strong translational potential as non-invasive biomarkers. EV-based liquid biopsy supports early cancer detection, disease monitoring, and prediction of therapeutic response. However, the clinical utility and validation of these EV-based biomarkers remain limited by EV heterogeneity, including tumour- versus non-tumour-derived EV populations, as well as pre-analytical and analytical variability in sample collection, processing, isolation, and characterisation. EVs also contribute to drug resistance while offering new therapeutic opportunities through engineered platforms for targeted delivery of drugs, RNA therapeutics, and immunomodulatory agents. Although encouraging findings have been reported in experimental and early clinical studies, most EV-based applications remain under investigation and require rigorous clinical validation before routine clinical implementation.