Journal
EUROPEAN JOURNAL OF CANCER
Volume 36, Issue 1, Pages 37-42Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0959-8049(99)00211-7
Keywords
5-fluorouracil; dihydropyrimidine dehydrogenase; oral chemotherapy
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More than 80% of an administered 5-fluorouracil (5-FU) dose is degraded by dihydropyrimidine dehydrogenase (DPD), making it an important regulator of this commonly used anticancer agent. The high variation in population DPD activity, association with 5-FU activity, and development of DPD inhibitors have all contributed to the current focus on this enzyme. This review details the impact of DPD on 5-FU pharmacology, catalogues recent information on DPD mutations, evaluates the case for tumour DPD as a source of 5-FU resistance and introduces the clinical case for DPD inhibitors as a mechanism for the use of oral fluoropyrimidine therapies. (C) 2000 Elsevier Science Ltd. All rights reserved.
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