Invited Speaker

Pharmacogenetics of Cytochrome 2D6: A Translational Medicine perspective
Imtiaz M. Shah
UK

With rapid scientific advances in the postgenomic era, pharmacogenomics has a crucial contribution to make to research in translational medicine. By using patient genomic information, this bench-to-bedside research approach aims to develop more effective targeting of drug therapy in clinical practice. One of the important areas of pharmacogenetic variability is in drug metabolism via the cytochrome P450 (CYP) enzyme system. The best-studied enzyme, Cytochrome 2D6 (CYP2D6) metabolises many commonly used medications and displays extensive genetic polymorphism. Important drug classes metabolised by CYP2D6, which have shown pharmacogenetic variability in clinical studies, are the antidepressants, antipsychotics, analgesics, cardiovascular drugs and the breast cancer drug, tamoxifen. The approval of CYP2D6 genotype testing (Amplichip^® CYP450) by the FDA in 2005 has put this enzyme at the forefront of research into personalised medicine. The recent elucidation of the CYP2D6 crystal structure is an important advance in the drug discovery process, as lead drug candidate optimisation includes defining its metabolism by CYP2D6 and inhibition of this enzyme. This lecture covers recent progress in CYP2D6 pharmacogenomics and its applications to translational medicine.