Dihydropyrimidine Dehydrogenase (DPD) and Thymidylate Synthase (TYMS) Germline Pharmacogenomics Role in Predicting Fluoropyrimidines Toxicity in Pa...

Date 29 June 2016
Event ESMO World Congress on Gastrointestinal Cancer 2016
Session ESMO World Congress on Gastrointestinal Cancer 2016 - Abstracts book
Presenter M. Khushman
Citation Annals of Oncology (2016) 27 (2): 1-85. 10.1093/annonc/mdw199
Authors M. Khushman1, P. Hosein2, D. Cameron1, D. Clarkson1, T. Butler1, M. Vu1, C. Norden1, W. Baliem1, V. Jones1, S. Bhadkamkar1, C. Nelson1, F. Lee1, A. Singh1, W. Taylor1
  • 1Mitchell Cancer Institute, The University of South Alabama, Mobile, Alabama, USA, /
  • 2The University of Kentucky, Lexington, Kentucky, USA, /


Fluoropyrimidines (5-Fluorouracil, Capecitabine and Tegafur) are antimetabolites that target the S phase of the cell cycle. The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits TYMS, thus preventing DNA synthesis and ultimately cell death. While controversy exists in the literature, low expression of TYMS predicts increased toxicity to Fluoropyrimidines. DPD is the rate-limiting enzyme for fluoropyrimidine catabolism and eliminates >80% of administered 5-fluorouracil. DPD deficiency is a pharmacogenetic syndrome associated with dose-limiting toxicity to fluoropyrimidines. In patients who are deficient in DPD, 5-fluorouracil can be fatal or cause profound toxicity. Herein we describe our experience with DPD and TYMS germline pharmacogenomics role in predicting fluoropyrimidines toxicity in patients with GI malignancies.