Pretreatment DPYD/DPD Testing: Clinical Updates and Considerations

In this lecture, Dr. Yuan Ji focuses on pretreatment DPYD/DPD testing, one of the most extensively discussed or debated topics in clinical pharmacogenomics (PGx) implementation and oncology practice in recent years. Centered with real patient stories and the devastating fluoropyrimidines (FPs) toxicity-related mortality rate, Dr. Ji explains the basics of clinical pharmacology of FPs, in relation to the severe, sometimes life-threatening treatment-related toxicities in genetically predisposed dihydropyrimidine dehydrogenase (DPD)-deficient patients and the importance of performing pretreatment DPYD/DPD testing in all FPs-treated patients.

Additionally, Dr. Ji also reviews the history of the FDA's labeling updates for FPs, available dosing guidelines, and resources for clinical implementation of DPYD genotype-guided dosing practice of FP treatment and shares her insights on the Association for Molecular Pathology (AMP) PGx Working Group recommendation on DPYD genotyping alleles that aims to address the heterogeneity among clinical DPYD genotyping tests and to promote testing standardization across clinical laboratories. Lack of carefully designed and comprehensive DPYD testing with short turnaround time has been one of the several concerns of oncologists, impeding the clinical adoption of pretreatment DPYD/DPD testing for all cancer patients who hope to be cured rather than to be harmed by the toxicities of their chemotherapy medications.

Originally published on September 2, 2025

Lecture Presenter

Yuan Ji, PhD, DABCP, FACMG Associate Professor University of Utah School of Medicine Medical Director, Molecular Genetics and Genomics ARUP Laboratories

Dr. Yuan Ji is a medical director in Molecular Genetics and Genomics at ARUP Laboratories and an associate professor of pathology at the University of Utah School of Medicine. She received her PhD in molecular pharmacology and experimental therapeutics at the Mayo Clinic in Rochester, Minnesota, where she further completed her postdoctoral research fellowship in pharmacogenomics, an NIH-T32 Clinical Pharmacology fellowship and an ABMGG fellowship in clinical molecular genetics. Dr. Ji received multiple early career development awards and grants, including an NIH-KL2 Mentored Career Award and a Minnesota Partnership for Biotechnology and Medical Genomics Award. Dr. Ji is board certified in both clinical pharmacology and medical genetics and genomics. Dr. Ji’s major clinical and research focus is in pharmacogenomics, i.e., identifying novel pharmacogenomics markers and accurately testing, interpreting, and reporting pharmacogenomic variants. In addition, Dr. Ji also developed a vast interest in developing cost-effective diagnostic testing for diseases including somatic overgrowth and related syndromes.

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Objectives

After this presentation, participants will be able to:

• Review FPs, DPD, and DPD deficiency
• Describe the association of DPYD variants with FP-related toxicities
• Clarify updates on professional guidelines and clinical practices
• Review heterogeneity among clinical pharmacogenomic genotyping tests and introduce the AMP PGx Working Group recommendation on DPYD genotyping alleles
• Discuss additional considerations of implementing clinical DPYD/DPD testing

Sponsored by:

University of Utah School of Medicine, Department of Pathology, and ARUP Laboratories