Role of extracellular vesicle derived biomarkers in drug metabolism and disposition

Zivile Useckaite, A. David Rodrigues, Ashley Hopkins, Lauren A. Newman, Jillian G. Johnson, Michael Sorich, Andrew Rowland

Research output: Contribution to journalReview articlepeer-review

Abstract

Extracellular vesicles (EVs) are small, non-replicating, 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 non-vesicular contaminants such as apoptotic bodies, plasma proteins and lipoproteins that are routinely co-isolated with EVs albeit to a different extent depending on the isolation technique. The following mini-review summarises 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 (MISEV) and EV Track reporting standards are summarised 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 aetiology. 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.
Original languageEnglish
Article numberDMD-MR-2021-000411
JournalDrug Metabolism and Disposition
Volume49
Issue number8
DOIs
Publication statusPublished - 1 Aug 2021

Keywords

  • Cytochrome P450 (CYP)
  • drug metabolism
  • glucuronidation/UDP-glucuronyltransferases/UGT
  • transporters

Fingerprint

Dive into the research topics of 'Role of extracellular vesicle derived biomarkers in drug metabolism and disposition'. Together they form a unique fingerprint.

Cite this