TY  - JOUR
AU  - Tremmel, Roman
AU  - Hofmann, Ute
AU  - Haag, Mathias
AU  - Schaeffeler, Elke
AU  - Schwab, Matthias
TI  - Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes.
JO  - Annual review of pharmacology and toxicology
VL  - 64
SN  - 0362-1642
CY  - Palo Alto, Calif.
M1  - DKFZ-2023-01669
SP  - 65-87
PY  - 2024
N1  - 2024 Jan 23;64:65-87
AB  - Pharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype concordance is limited. Thus, we discuss different phenotyping strategies using exogenous xenobiotics (e.g., drug cocktails) or endogenous compounds for phenotype prediction. In particular, minimally invasive approaches focusing on liquid biopsies offer great potential to preemptively determine metabolic and transport capacities. Early studies indicate that ADME phenotyping using exosomes released from the liver is reliable. In addition, pharmacometric modeling and artificial intelligence improve phenotype prediction. However, further prospective studies are needed to demonstrate the clinical utility of individualized treatment based on phenotyping strategies, not only relying on genetics. The present review summarizes current knowledge and limitations. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
LB  - PUB:(DE-HGF)16
C6  - pmid:37585662
DO  - DOI:10.1146/annurev-pharmtox-032023-121106
UR  - https://inrepo02.dkfz.de/record/278588
ER  -