Role of Extracellular Vesicle-Derived Biomarkers in Drug Metabolism and Disposition

Abstract

Extracellular vesicles (EVs) are small, nonreplicating, lipid-encapsulated particles that contain a myriad of protein and nucleic acid cargo derived from their tissue of origin. The potential role of EV-derived biomarkers to the study of drug metabolism and disposition (DMD) has gained attention in recent years. The key trait that makes EVs an attractive biomarker source is their capacity to provide comparable insights to solid organ biopsy through an appreciably less invasive collection procedure. Blood-derived EVs exist as a heterogenous milieu of biologically distinct particles originating from different sources through different biogenesis pathways. Furthermore, blood (plasma and serum) contains an array of vesicular and nonvesicular contaminants, such as apoptotic bodies, plasma proteins, and lipoproteins that are routinely coisolated with EVs, albeit to a different extent depending on the isolation technique. The following minireview summarizes current studies reporting DMD biomarkers and addresses elements of EV isolation and quantification relevant to the application of EV-derived DMD biomarkers. Evidence based-best practice guidance aligned to Minimum Information for the Study of Extracellular Vesicles and EV-TRACK reporting standards are summarized in the context of DMD studies. SIGNIFICANCE STATEMENT: Extracellular vesicle (EV)-derived protein and nucleic acid cargo represent a potentially game-changing source of novel DMD biomarkers with the capacity to define within- and between-individual variability in drug exposure irrespective of etiology. However, robust translation of EV-derived biomarkers requires the generation of transparent reproducible evidence. This review outlines the critical elements of data generation and reporting relevant to achieving this evidence in a drug metabolism and disposition context.