The Broader Context of Liquid Biopsy in Absorption, Distribution, Metabolism, and Elimination

We read with interest the manuscript of Pridgeon and colleagues entitled “Liquid Biopsies or Therapeutic Drug Monitoring for CYP Activity Profile Determination.” Given the title of the manuscript it is notable that no experiments evaluating the performance of either liquid biopsy or therapeutic drug monitoring (TDM) approaches to determine cytochrome P450 (CYP) activity are described. Rather the manuscript describes a set of in vitro analyses that confirm a weak correlation between messenger RNA (mRNA) and protein expression for CYP within human liver tissue. By extrapolation, the authors infer but do not demonstrate poor performance for mRNA-based liquid biopsies. We acknowledge and agree that confirmation of prior findings in human liver tissue of the relatively weak correlation between CYP mRNA and protein expression does highlight the need for validation studies for mRNA-based liquid biopsies.

However, Pridgeon and colleagues conflate the general concept of a liquid biopsy with one specific implementation using mRNA...