Multi-omics analysis of extracellular vesicle cargo in cancer

Extracellular vesicles (EVs) are increasingly recognized as minimally invasive sources of molecular information in cancer, carrying nucleic acids, proteins, lipids, and metabolites that reflect tumor biology. Recent advances in high-throughput sequencing and mass spectrometry have not only enabled multi-omics profiling of EV cargo but also revealed that different molecular layers capture distinct yet complementary aspects of cancer processes. This review provides a comprehensive overview of the rapidly expanding landscape of EV multi-omics, highlighting methodological constraints, the predominance of proteo-transcriptomic analyses, and the principal strategies used for multi-omics layer data integration. We outline how these developments refine biomarker discovery, expose new mechanistic insights, and emphasize the need for standardized, multi-analyte EV workflows to fully realize their clinical and translational potential.