Prof Howard McLeod

Title: Using the genome to guide therapy

The field of pharmacogenomics has seen some exciting advances in the recent past. The Human Genome Project and International HapMap projects have uncovered a wealth of information for researchers. This has lead to the discovery of clinically predictive germline genotypes (e.g. UGT1A1*28-irinotecan, TYMS TSER-fluoropyrimidines, CYP2D6-tamoxifen, CYP2C19-clopidogrel), germline haplotypes (e.g. VKORC1 Haplotype A-warfarin) and somatic mutations (e.g. epidermal growth factor receptor-gefitinib/erlotinib, KRas-cetuximab/panitumumab). The introduction of FDA approved pharmacogenetic tests (UGT1A1*28, CYP2C9/VKORC1, CYP2D6/CYP2C19) and the initiation of genotype-guided clinical trials have provided the first steps towards the integration of pharmacogenomics into clinical practice. It is also clear that there are many non-scientific barriers to clinical application. These include integration of new tests into health systems, changing old habits to allow application of new data, and the reality that the cost of both testing and the therapeutic options are a key driver in health care. As the scientific evidence matures, A team research approach must be more aggressively applied in order to overcome the many obstacles to delivering more careful selection of drug therapy.