Pharmacogenomic Profiling of ADME Gene Variants: Current Challenges and Validation Perspectives

In the past decades, many efforts have been made to individualize medicaltreatments, taking into account molecular profiles and the individual geneticbackground. The development of molecularly targeted drugs and immunotherapy have revolutionized medical treatments but the inter-patient variability in theanti-tumor drug pharmacokinetics (PK) and pharmacodynamics can be explained, atleast in part, by genetic variations in genes encoding drug metabolizing enzymes and transporters (ADME) or in genes encoding drug receptors. Here, we focus onhigh-throughput technologies applied for PK screening for the identification ofpredictive biomarkers of efficacy or toxicity in cancer treatment, whoseapplication in clinical practice could promote personalized treatments tailoredon individual's genetic make-up. Pharmacogenomic tools have been implemented and the clinical utility of pharmacogenetic screening could increase safety inpatients for the identification of drug metabolism-related biomarkers for apersonalized medicine. Although pharmacogenomic studies were performed in adultcohorts, pharmacogenetic pediatric research has yielded promising results.Additionally, we discuss the current challenges and theoretical bases for theimplementation of pharmacogenetic tests for translation in the clinical practice taking into account that pharmacogenomics platforms are discovery oriented andmust open the way for the setting of robust tests suitable for daily practice.