EV Translational Horizons as Viewed Across the Complex Landscape of Liquid Biopsies.

Extracellular Vesicle (EV)-based diagnostic and therapeutic tools are an area of intensive study and substantial promise, but EVs as liquid biopsies have advanced years ahead of EVs as therapeutic tools. EVs are emerging as a promising approach for detecting tumors, evaluating the molecular profiles of known disease, and monitoring treatment responses. Although correlative assays based on liquid biopsies are already having an impact on translational studies and clinical practice, much remains to be learned before these assays will be optimized for clinical correlations, functional biological studies, and therapeutic use. What follows is an overview of current evidence supporting the investigation and use of liquid biopsies, organized by specific liquid biopsy components available for analysis, along with a summary of what challenges must be overcome before these assays will provide functional biological insights into the pathogenesis and treatment of disease. The same challenges must also be overcome before it will be feasible to measure and monitor the dosing, distribution, pharmacokinetics, and delivery of EV therapeutics and their cargo in complex biofluids where EVs and circulate with and are co-isolated with a number of other nanoscale materials, including lipoproteins (LPPs), ribonucleoprotein complexes (RNPs), and cell free nucleic acids (cfNA).