Pharmacogenomics Biomarker Discovery and Validation for Translation in Clinical Practice

Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics(PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encodingdrug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encodingdrug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs andthe current knowledge of genome-disease and genome-drug interactions offers the opportunity to optimize tailored drugtherapy. High-throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validationfollowed by clinical-grade assay development and must comply to stringent regulatory guidelines. We here discuss themethodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroadamong molecular genetics, bioinformatics, and clinical medicine.