The research laboratory of Robert B. Diasio, M.D., at Mayo Clinic in Rochester, Minn., is focused on cancer pharmacogenetics and pharmacogenomics. Specifically, the laboratory examines the role played by genetics and genomics in whether cancer chemotherapy or targeted therapy produce cytotoxic or cytocidal effects in either normal host cells or tumor cells.
To better understand the basis for differences in drug response of normal or tumor cells, Dr. Diasio's laboratory is studying the effect of mutations in critical genes, such as those that are drug targets or involved in drug metabolism.
In normal host cells, Dr. Diasio's laboratory is interested in which mutations determine toxicity, while in tumor cells, the lab would like to know which mutations determine whether a particular anti-tumor agent is effective or ineffective in controlling tumor growth or killing the tumor.
Ultimately, Dr. Diasio's laboratory wants to use this information to develop molecular diagnostic tests, which would be used to simultaneously screen for multiple mutations important to drug activity before the drug is administered to a patient.
Such tests would make it possible to optimize therapy for an individual cancer patient. For example, an oncologist would know — prior to administering the first dose — whether he or she should give an increased or decreased dose of a particular drug to a particular patient.
In developing this pharmacogenetic approach, the laboratory has initially focused on one of the most commonly used cytotoxic cancer chemotherapy drugs, 5-fluorouracil (5-FU). Dr. Diasio's laboratory, which helped characterize the pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency, was among the first to demonstrate the importance of mutations in the gene coding for the important 5-FU metabolic enzyme DPD. This provided a better understanding of how 5-FU dosage should be regulated in the individual patient.