Pharmacogenomics in Drug Discovery and Development

Barkur S Shastry, Barkur S. Shastry, Shastry, Barkur S.

In the past several years, human genetics studies have progressed from monogenic to complex and common diseases because of the advancement in technologies. There is increased knowledge of the pharmacokinetics and pharmacogenomics of the drugs in adults as well as in children. These technological developments provided new diagnostic, prognostic, and therapeutic opportunities. We are now in a position to address many additional ambitious questions. For instance, in clinical medicine, interindividual variation in drug response is a major problem. Some of the heterogeneity of drug safety and efficacy among individuals can be explained by pharmacogenomics. It has also the potential to improve the treatment in both adults and children. In pediatrics however, there is ontogeny and metabolic capacity in children is different compared to adults. Several specific developmental changes may underlie some of the variability in drug response seen in children. They may also be responsible for adverse drug reactions (ADRs). Therefore, much of the diversity in drug effects cannot be explained by studying the genomic diversity alone. It is necessary to include the effect of growth (involves variations in gene expression) along with genetic differences when explaining the variability in treatment response. In this respect epigenomics may expand the scope of pharmacogenomics towards optimization of drug therapy. Future studies must focus on periods of maturation of the drug-metabolizing enzymes and polymorphisms in their genes by using candidate gene approach, gene expression analysis, genome-wide haplotype mapping, and proteomics. The integration of genetic data and clinical phenotypes along with the role of other factors is necessary to evaluate both efficacy and ADRs of any drug. It may require extensive genetic epidemiological studies spanning over many years.