High-Throughput Platforms in Drug Metabolism and Transport Pharmacogenetics

Although there are now several thousand published studies that have examined the genetic contribution to interindividual variation in drug treatment (i.e., pharmacogenetics), very few have examined the large portions of the genome; rather these have focused on candidate gene and pathway-based study designs. However, multiple large-scale genotyping technologies have recently emerged that allow the researcher to examine pharmacogenetic endpoints ~100–500,000 SNPs at a time. Each genotyping platform is slightly different and applicable to either the clinical setting, wherein the genetic information informs treatment in patients with certain variants, or the research setting, where patients that are treated with certain drugs are either prospectively or retrospectively evaluated for genetic variants that may influence treatment outcomes. The purpose of this chapter is to describe the current study designs in pharmacogenetics, the major findings of these studies that are applied clinically, to provide an overview of commercially available large-scale genotyping technologies, and to discuss how these technologies can be applied in both clinical and research settings. While oncology agents will be the primary focus of this chapter, given that individuals undergoing therapy for cancer are often treated with multiple drugs, it is important to also consider other agents.