Dihydropyrimidine Dehydrogenase (Dpyd) Gene Polymorphism: Portrait of a Serial Killer

  • Joseph Ciccolini
  • Cédric Mercier
  • Gérard Milano
Part of the Cancer Drug Discovery and Development™ book series (CDD&D)

Summary

Fluoropyrimidines (e.g., 5-FU, oral capecitabine) remain unchallenged as reference drugs for treating numerous solid tumors in adults, including digestive, head and neck, and breast cancers. The wide inter-patient variability observed in the pharmacokinetic profiles of these drugs is mainly caused by the erratic activity of dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for fluoropyrimidines catabolism. Beside circadian variations, DPD activity can be affected as well by DPYD gene polymorphisms, and genetic and epigenetic regulations, both in the liver and at the tumor site, which can have a strong impact on drug-induced toxicities and/or treatment outcome. In this respect, studying the causes of DPD deficiency allows for better understanding of the pharmacodynamics of 5-FU and capecitabine. Consequently, several strategies have been proposed to predict and anticipate the impact of variations in DPD on the clinical outcome of cancer patients receiving fluoropyrimidine chemotherapy.

Key Words

Fluoropyrimidines pharmacogenetics pharmacokinetics 

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Joseph Ciccolini
    • 1
  • Cédric Mercier
    • 2
  • Gérard Milano
    • 3
  1. 1.Pharmacokinetics–Medical OncologyUniversitéde la MéditerranéeMarseilleFrance
  2. 2.Medical OncologyUniversité de la MéditerranéeMarseilleFrance
  3. 3.Laboratoire d’Oncopharmacologie Centre Antoine LacassagneNiceFrance

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