Role of thymidine phosphorylase in biomodulation of fluoropyrimidines

Thymidine phosphorylase (TP) is a key enzyme in the activating pathway of 5'DFUR and capecitabine. On the other hand, TP is identical to platelet-derived endothelial cell growth factor (PD-ECGF) which is known to be an angiogenic factor. Recent studies show TP expression is increased in various malignancies compared with the surrounding normal tissues. These reports demonstrate that elevated TP expression indicates a predisposition for aggressive disease and/or poor prognosis. Therefore, it is a reasonable strategy to target TP in cancer treatment by using fluoropyrimidines including 5-fluorouracil (5FU), 5'DFUR and capecitabine. TP-mediated biomodulation of fluoropyrimidines to enhance their anti-tumor effects has been investigated. TP up-regulators including cytokines, anti-tumor drugs and X-ray irradiation significantly increase cytotoxicity of fluoropyrimidines. Also, transfection of TP cDNA significantly enhances cytotoxicity of fluoropyrimidines. Biomodulation of fluoropyrimidines is clinically successful in treating some malignancies. We report a review on roles of TP in biomodulation of fluoropyrimidines.