Role of Platelet Derived Endothelial Cell Growth Factor/Thymidine Phosphorylase in Fluoropyrimidine Sensitivity and Potential Role of Deoxyribose-1-phosphate

Thymidine phosphorylase (TP) catalyzes the phosphorolytic cleavage of thymidine (TdR) to thymine and deoxyribose‐1‐phosphate (dR‐1‐P). TP, which is overexpressed in a wide variety of solid tumors, is involved in the activation and inactivation of fluoropyrimidines. We investigated the role of TP in 5′‐deoxy‐5‐fluorouridine (5′DFUR), 5‐fluorouracil (5FU) and trifluorothymidine (TFT) sensitivity. TP had no effect on TFT while it activated 5′DFUR and to a lesser extent 5FU. In order to provide an explanation for this difference in activation of 5′DFUR and 5FU, we studied the role of the 5FU co‐substrate, dR‐1‐P, needed for its activation.