Overlapping effects of genetic variation and epigenetics on drug response: Challenges of pharmacoepigenomics

摘要

The influence of genetic variants on drug response is becoming increasingly better understood. In particular, genetic variants in drug-metabolizing enzymes and drug transporters and also mutations of the tumor genome (e.g., in tyrosine kinase signaling pathways) have been extensively characterized in vitro and in vivo. Whereas the consideration of genomic biomark-ers is crucial in modern oncologic approaches, so far for non-oncologic diseases, only a few drug-related genetic biomarkers can be translated into clinical practice. Clear pharmacokinetic consequences have been derived (e.g., for genetic variants in drug-metabolizing enzymes), leading to complete or severe loss of function as in the cases of phase I enzymes, such as CYP2D6, or the phase II enzyme TPMT.