Predicting adverse 5-fluorouracil (5-FU) toxicity
Ongoing studies in my lab are directed toward developing predictive tests for adverse 5-FU toxicity using a combination of biochemical, cellular, model organism and clinical studies to identify relevant biomarkers of toxicity risk.
5-fluorouracil is a cytotoxic chemotherapy drug that is prescribed to nearly 300,000 cancer patients in the United States each year for the treatment of aggressive cancers, such as colorectal cancer, breast cancer, and head and neck cancer.
My lab was among the first to demonstrate the importance of dihydropyrimidine dehydrogenase (DPD) as a critical determinant of 5-FU exposure levels. We subsequently demonstrated that specific genetic variations in DPYD, the gene encoding DPD, are deleterious to DPD function and act as predictive markers of risk of 5-FU-related adverse toxicity.