Abstract
Pharmacogenomics (PGx) entails the study of heritability of drug response. This may include both variability in genes related to pharmacokinetics (drug absorption, distribution, metabolism and excretion) and pharmacodynamics (e.g., drug receptors or signaling pathways). Individualizing drug therapy taking into account the genetic profile of the patient has the potential to make drug therapy safer and more effective. Currently, this approach relies on the determination of genetic variants in pharmacogenes by genotyping. However, it is widely acknowledged that large variability in gene expression is attributed to non-structural genetic variants. Therefore, at least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting. Extracellular vesicles (EVs) are lipid encapsulated structures that contain cargo such as lipids, nucleic acids and proteins. Since their cargo is tissue- and cell-specific they can be used to determine the expression of pharmacogenes in the liver. In this review, we describe methods of EV isolation and the potential of EVs isolated from liquid biopsies as a tool to determine the expression of pharmacogenes for use in personalized medicine.
Highlights
Pharmacogenomics (PGx) is the study of genetic variation underlying variability in drug response [1]
Variation in genes that encode for drug metabolizing enzymes, drug transporters, drug receptors or proteins involved in signaling pathways contribute to interindividual variability of drug response
At least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting
Summary
Pharmacogenomics (PGx) is the study of genetic variation underlying variability in drug response [1]. One may use the phenotype of a pharmacogene to apply personalized medicine In this approach the so called endophenotype [5], such as drug concentration in plasma or urine following administration of a drug probe, is determined as an indirect measure of drug metabolic enzyme activity. At least from a theoretical viewpoint individualizing drug therapy based upon expression of pharmacogenes rather than on genotype may be advantageous but has been difficult to implement in the clinical setting. To this end, the use of extracellular vesicles (EVs) isolated from liquid biopsies are of great interest. Background of EVs and methods for isolation and characterization of EVs from liquid biopsies and their application to determine the RNA and protein expression of pharmacogenes in the liver will be discussed and presented as an innovative method for future application in personalized medicine
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