RIKEN Omics Science Center, Japan
Toshihisa Ishikawa was Professor of Biochemistry, Molecular Biology and Pharmacogenomics at Tokyo Institute of Technology (200-2009) and is Senior Scientist at Omics Science Center RIKEN Yokohama Institute (2009-present) in Japan. He served as a member of the Steering Committee of the FDA Critical Path Transporter Workshop in 2008. Presently, Ishikawa is a member of the Emerging Issues Committee of the International Transporter Consortium. Most recently, Ishikawa has been elected as Chairman for the 2015 Gordon Research Conference on “Multi-Drug Efflux Systems.”
Accumulating evidence strongly suggests that genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets are linked to inter-individual differences in the efficacy and toxicity of many medications. During past two decades, the role of carrier-mediated transport in determining the pharmacokinetics of drugs has becoming increasingly evident with the discovery of genetic variants that affect expression and/or function of a given drug transporter. Drug transporters are expressed at numerous epithelial barriers, such as intestinal epithelial cells, hepatocytes, renal tubular cells and at the blood-brain barrier. Pharmacogenomic studies are rapidly elucidating the inherited nature of differences in pharmacokinetic and pharmacodynamic effects, thereby enhancing drug discovery and providing a stronger scientific basis for optimizing drug therapy on the basis of each patient’s genetic constitution. Hitherto researchers have associated alterations in drug uptake and/or disposition with the presence of genetic polymorphisms. The International Transporter Consortium (ITC) has most recently published the FDA Whitepaper as a report from the FDA Critical Path Initiative-sponsored Drug Transporter Workshop (Nature Review Drug Discovery, 9, 215-236, 2010). The pharmaceutical regulatory authorities are now requesting that drug companies integrate genetic information into their clinical trial design. In this context, pharmacogenomics of drug transporters is recognized increasingly important. A key requirement for the development of personalized medicine, however, is the ability to rapidly and conveniently test patients for genetic polymorphisms and/or mutations. We will discuss pharmacognomics of drug transporters as well as emerging new technologies for SNP detection and clinical applications.