Pharmacogenomics: basis and milestones

Abstract

The genomic interindividual heterogeneity for proper pharmacotherapy remains a significant challenge for research, clinical decision-making, and the design of clinical trials. Translation of the obtained genomic information into actionable clinical advice lags behind, mainly due to insufficient powered and representative trials that can quantify the added value of pharmacogenetic/pharmacogenomic research, the pharmacogenetic complexity of rare variants with unclear functional consequences, the effect of environmental/nutritional factors, and the diversity of the populations worldwide. In this respect, pharmacogenetics and pharmacogenomics (PGx) are emergent fields aimed at tailoring the patient therapy. Both are disciplines with overlapping aims, with the latter being newer and broader than the former. Pharmacogenetics has mainly focused on single genetic variations which can influence responses to drugs (gene-drug pairs), while pharmacogenomics has focused on how all genes, the genome, interact with the action of drugs [1]. Clinical research has demonstrated the cost-effectiveness of pharmacogenetic testing in improving drug compliance in patients, leading to decreased hospital admissions due to adverse reactions to medication [2, 3]. Besides, in the last years, a new promising field has addressed to the study about how environmental factors influence the differential expression of genes related to drug response; this new area is called pharmacoepigenetics [4]. In this chapter, we focus on basic concepts and milestones of these areas.