Pharmacogenetics and Pharmacogenomics II: Genetic Determinants of Drug Responses and Adverse Drug Reactions

The ability to predict efficacy and safety is crucial for drug discovery and development. To date, there are only a few genetic biomarkers whose clinical validity in predicting drug response has been clearly established; for example, HER-2/neu-positivity in breast cancer as a predictor of response to trastuzumab (Herceptin) [1]. Patient variability in response to medications can range from failure to demonstrate an expected therapeutic effect to development of an adverse reaction, resulting in significant patient morbidity and mortality, as well as increasing healthcare costs. In order to optimize treatment response and decrease adverse drug reactions, pharmacogenetics and pharmacogenomics are being increasingly utilized. Pharmacogenetics is the study of genetic variation and its effects on the response to drugs, vaccines, or other pharmaceutical agents [2]. Pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. Primary candidate genes of interest include those encoding for drug receptors, metabolizing enzymes, and transporters. However, selection of optimal drug therapy may also involve disease susceptibility genes indirectly affecting drug responses [3].