Current perspective on pediatric pharmacogenomics.

Pharmacogenomics (PG) studies the influence of genetic variations on treatment outcomes and aims to provide safer and more effective therapies by using genetic data to guide the choice of medication and the dosing regimen. Treatment associated toxicity in children can be severe and long lasting. Finding the right dose in children is a sensitive and complicated process as they display age-dependant pharmacokinetics due to differential organ maturation and enzymatic switches. We use examples from different treatment areas to show the impact of genetic variations on the therapeutic responses such as cytochrome P450 3A5 (CYP3A5) and Tacrolimus dosing, codeine and CYP2D6 gene variants, 6-mercaptopurine toxicity due to mutations in the thiopurine methyltransferase (TPMT) gene. The examples of Asparaginase and Carbamazepine are also shortly discussed. The results of some case reports and clinical trials that investigated the effect of genetic variation in those genes on the clinical outcome are briefly highlighted. Pharmacogenomics can increase the efficacy and safety of existing drug dosing algorithms but replication studies and prospective clinical trials demonstrating the advantage of pharmacogenomics-guided therapies over current standards-of-care are strongly needed. Guidelines and recommendations are emerging through different agencies to assist clinicians in making therapeutic decisions based on genetic data.