Thymidine phosphorylase: its role in sensitivity and resistance to anticancer drugs

Abstract

Thymidine phosphorylase (TP) is an angiogenic enzyme present in normal tissues. Increased levels are found in many tumors, in stromal cells, tumor cells or both. High tumor TP levels may confer a poor prognosis. Cytokines (including interferons), tissue hypoxia and low pH increase TP levels. The influence of tumor TP on fluoropyrimidine toxicity is variable, but capecitabine is a prodrug of fluorouracil that requires activation by TP and hence may have a higher therapeutic index than other fluoropyrimidines. Folate-based thymidylate synthase inhibitors may also be more effective in tumors with a high TP because of increased degradation of endogenous thymidine. Copyright 1999 Harcourt Publishers Ltd.