Abstract
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).
Highlights
Cells of all types produce a number of secreted or shed macromolecular complexes that can be examined for liquid biopsies
Liquid biopsies may offer a more comprehensive overview of a tumor’s molecular landscape due to the integrative nature of an assay of biomarkers that are detectable in biofluid samples, as compared to the focused interrogative view that is obtained by a tissue biopsy that views only part of a tumor
The complexity of the many facets to be considered in rigorous characterization of extracellular vesicles (EVs) from biofluids provides an informative perspective on the complexities that remain to be tackled when considering methods for monitoring delivery, circulation, kinetics, and clearance of EVbased therapeutics. (Autio et al, 2014; Dittamore et al, 2014; Scher et al, 2016, 2017; Lack et al, 2017; Figueroa and Carter, 2018; Armstrong et al, 2019; Salami et al, 2019)
Summary
Cells of all types produce a number of secreted or shed macromolecular complexes that can be examined for liquid biopsies. The types of biomarkers available in biofluids are highly diverse and include circulating tumor cells (CTCs), cell free nucleic acids (cfNA), lipoprotein particles (LPP), extracellular vesicles (EVs), and exomeres. CTCs carry an individually complete “package” of cellular cargo (proteins, nucleic acids, phospholipids, etc.), which reflects the composition of some part of a tumor, extracellular biofluid components are inherently fragmentary. In other words, these biofluid components individually are only partial representations of the cell from whence they originated, but these components can be analyzed to interrogate the status of the tumor
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