We analyzed the pyrimidine metabolite in the urine of a patient with severe mucositis and hand and foot syndrome, who was administered 5-fluorouracil for recurrence of gastric cancer. From our analysis, it was suggested that the patient had decreased dihydropyrimidine dehydrogenase activity. Dihydropyrimidine dehydrogenase activity is usually measured in peripheral blood mononuclear cells, but this time it was estimated from the analysis of uracil, dihydrouracil, thymine, and dihydrothymine in the urine. We concluded that urinary analysis of the pyrimidine metabolism is effective as screening for the prediction and prevention of 5-fluorouracil toxicity.
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World J Gastrointest Oncol
January 2025
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Campania, Italy.
Background: Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the gene. About 7% of the European population is a carrier of gene polymorphisms associated with reduced DPD enzyme activity.
Aim: To assess the prevalence of polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.
Cureus
December 2024
Oncology, Qiannan People's Hospital, Duyun, CHN.
Capecitabine is an oral prodrug metabolized into 5-fluorouracil (5-FU) and serves as a representative anticancer agent. While fluoropyrimidine treatment is usually well-tolerated, a subset of patients unfortunately experiences severe and sometimes life-threatening toxicity related to these compounds. This adverse reaction is frequently attributed to partial or complete deficiencies in the dihydropyrimidine dehydrogenase (DPD) enzyme.
View Article and Find Full Text PDFJ Adv Res
January 2025
Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, Beijing, China. Electronic address:
Introduction: Dihydropyrimidine dehydrogenase (DPD) is a major determinant of cancer 5-fluorouracyl (5-FU) resistance via its direct degradation. However, the mechanisms of tumoral DPD upregulation have not been fully understood.
Objectives: This study aimed to explore the role of S1PR2 in the regulation of tumoral DPD expression, identifying S1PR2 as the potential target for reversing 5-FU resistance.
Cancer Chemother Pharmacol
January 2025
Service de Génomique des Tumeurs et Pharmacologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France.
The enzyme dihydropyrimidine dehydrogenase (DPD) is the primary catabolic pathway of fluoropyrimidines including 5 fluorouracil (5FU) and capecitabine. Cases of lethal toxicity have been reported in cancer patients with complete DPD deficiency receiving standard dose of 5FU or capecitabine. DPD is encoded by the pharmacogene DPYD in which more than 200 variants have been identified.
View Article and Find Full Text PDFOncol Lett
February 2025
Division of Surgery, Orthopaedics and Oncology, Department of Biomedical and Clinical Sciences, Linköping University, SE-58185 Linköping, Sweden.
Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and biomarkers to guide treatment decisions in PDAC are generally lacking. Intratumoural expression of dihydropyrimidine dehydrogenase (DPD) is a potential prognostic parameter in patients with PDAC undergoing surgical resection and postoperative chemotherapy. In the present study, DPD was analysed by immunohistochemistry of a tissue microarray platform including a real-world cohort of 495 patients with PDAC who had undergone resection with curative intent at any of three tertiary centres, including Northern, Western and Southeastern regions of Sweden, between 1993 and 2019.
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