Drug methylation in cancer therapy: lessons from the TPMT polymorphism

The genetic polymorphism of thiopurine methyltransferase (TPMT) is one of the most developed examples of pharmacogenetics, spanning from molecular genetics to clinical diagnostics for individualizing thiopurine therapy (i.e. azathioprine, mercaptopurine, and thioguanine). Elucidation of the molecular mechanisms and biochemical consequences of TPMT deficiency demonstrates how pharmacogenetic traits can be identified, characterized, and translated to the bedside. Insights gained from studies of the TPMT polymorphism illustrate the potential of pharmacogenomics to optimize cancer therapy by avoiding toxic side effects in genetically distinct subgroups of patients.