Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics

Leiden Repository

Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics

Type: Doctoral Thesis
Title: Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics
Author: Lunenburg, C.A.T.C.
Issue Date: 2019-06-11
Keywords: Fluoropyrimidines
5-fluorouracil
Capecitabine
DPYD
DPD
Dihydropyrimidine dehydrogenase
Pharmacogenetics
Pharmacogenomics
Personalised medicine
Abstract: Fluoropyrimidines, such as 5-fluorouracil (5-FU) and capecitabine, are among the most frequently prescribed anticancer drugs. They are inactivated by the enzyme dihydropyrimidine dehydrogenase (DPD). Up to 5% of the population is DPD deficient and these patients have a significantly increased risk of severe and potentially lethal toxicity when treated with regular doses of 5-FU or capecitabine. DPD is encoded by the gene DPYD and variants in DPYD can lead to a decreased DPD activity. Although prospective DPYD genotyping is a valuable tool to identify patients with DPD deficiency, and thus those at risk for severe and potential life-threatening toxicity, prospective genotyping has not yet been implemented in daily clinical care.With this thesis we improved knowledge on different aspects of DPYD genotyping and DPD phenotyping, in order to better predict DPD deficient patients and personalize their therapy. In addition, we improved clinical implementation of DPYD genotyping, and reduced the risk of severe fluoropyrimidine-induced toxicity in DPYD variant allele carriers.
Promotor: Supervisor: Gelderblom A.J., Guchelaar H.-J. Co-Supervisor: Swen J.J.
Faculty: Medicine / Leiden University Medical Center (LUMC)
University: Leiden University
Uri: urn:isbn:9789463325004
Handle: http://hdl.handle.net/1887/74404
 

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application/pdf Appendices 781.6Kb View/Open
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