Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance

Cancer-derived extracellular vesicles (EVs) have been detected in the bloodstream and other biofluids of cancer patients. They carry various tumor-derived molecules such as mutated DNA and RNA fragments, oncoproteins as well as miRNA and protein signatures associated with various phenotypes. The molecular cargo of EVs partially reflects the intracellular status of their cellular origin, however various sorting mechanisms lead to the enrichment or depletion of EVs in specific nucleic acids, proteins or lipids. It is becoming increasingly clear that cancer-derived EVs act in a paracrine and systemic manner to promote cancer progression by transferring aggressive phenotypic traits and drug-resistant phenotypes to other cancer cells, modulating the anti-tumor immune response, as well as contributing to remodeling the tumor microenvironment and formation of pre-metastatic niches. These findings have raised the idea that cancer-derived EVs may serve as analytes in liquid biopsies for real-time monitoring of tumor burden and drug resistance. In this review, we have summarized recent longitudinal clinical studies describing promising EV-associated biomarkers for cancer progression and tracking cancer evolution as well as pre-clinical and clinical evidence on the relevance of EVs for monitoring the emergence or progression of drug resistance. Furthermore, we outlined the state-of-the-art in the development and commercialization of EV-based biomarkers and discussed the scientific and technological challenges that need to be met in order to translate EV research into clinically applicable tools for precision medicine.