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5-fluorouracil and dihydropyrimidine dehydrogenase
1Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. tkubota@sc.itc.keio.ac.jp
International Journal of Clinical Oncology
|July 10, 2003
Summary
Dihydropyrimidine dehydrogenase (DPD) is crucial for 5-fluorouracil (5-FU) chemotherapy. Inhibiting DPD activity can reduce 5-FU toxicity and enhance its effectiveness in cancer treatment.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of fluoropyrimidines.
- DPD activity significantly influences the pharmacokinetics and toxicity of 5-fluorouracil (5-FU), a widely used chemotherapy drug.
- Tumor DPD activity affects 5-FU sensitivity, highlighting its clinical importance.
Purpose of the Study:
- To summarize the critical role of DPD in 5-FU cancer chemotherapy.
- To discuss the development and impact of DPD-inhibiting drugs.
- To highlight the clinical significance of DPD in optimizing 5-FU therapy.
Main Methods:
- Review of existing literature on DPD, 5-FU, and related drug development.
- Analysis of the enzymatic role of DPD in pyrimidine degradation.
- Examination of clinical implications of DPD activity and inhibition.
Main Results:
- DPD is the rate-limiting enzyme in (fluorinated) pyrimidine degradation.
- DPD activity directly impacts 5-FU pharmacokinetics, toxicity, and efficacy.
- DPD-inhibitory fluoropyrimidines offer improved oral 5-FU therapy by modulating DPD.
Conclusions:
- DPD plays a pivotal role in the clinical application of 5-FU chemotherapy.
- Targeting DPD activity represents a promising strategy to enhance cancer treatment outcomes.
- DPD-inhibitory fluoropyrimidines are valuable in managing 5-FU therapy for cancer patients.