The Dihydropyrimidine Dehydrogenase Deficiency Laboratory of Robert B. Diasio, M.D., at Mayo Clinic studies drug-related adverse toxicity, which is one of the most significant barriers preventing the delivery of chemotherapy doses that are effective against cancer.

Our lab studies interindividual differences in drug metabolism, which can serve to both activate and inactivate drugs, and drug uptake and excretion, which contribute to variability in response and toxicity to chemotherapeutics. We take a multifaceted approach to understanding these complex problems by using a broad array of model systems and clinical specimens to investigate genetic, epigenetic and biochemical pathways of drug toxicity and resistance.

Our lab was instrumental in identifying the dihydropyrimidine dehydrogenase (DPD) enzyme as a critical determinant of adverse toxicity to the commonly used chemotherapy drug 5-fluorouracil (5-FU). DPD rapidly inactivates approximately 85% of 5-FU in the liver within minutes of drug administration. Our lab also undertook a comprehensive study of genetic variants in the gene encoding DPD for their effect on 5-FU inactivation using a combination of in vitro, cellular and clinical studies. We also identified and characterized clinically relevant mechanisms by which DPD expression is controlled.

We're expanding these methodologies to evaluate pharmacological pathways relevant to additional chemotherapies. We expect that these studies will make possible precision medicine-based approaches to individualize anti-cancer treatments to maximize drug efficacy while minimizing adverse toxicity.

Dr. Diasio's laboratory is affiliated with the Mayo Clinic Cancer Center — Research.

About Dr. Diasio

In addition to his extensive career as a researcher and principal investigator of the Dihydropyrimidine Dehydrogenase Deficiency Lab, Dr. Diasio is a professor of pharmacology at Mayo Clinic College of Medicine and Science in Rochester, Minnesota. Dr. Diasio also spent nearly 15 years as director of Mayo Clinic Cancer Center, stepping down in February 2020 to focus on his research. Dr. Diasio's goal is to improve the understanding of drug metabolism and help pave the way for improved personalized cancer treatments.

Read more about Dr. Diasio's research and clinical studies.