Targeting platelet-derived endothelial cell growth factor/thymidine phosphorylase for cancer therapy

Biochem Pharmacol. 2007 Dec 3;74(11):1555-67. doi: 10.1016/j.bcp.2007.05.008. Epub 2007 May 16.


Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine nucleoside salvage pathway, but it also recognizes and inactivates various anti-cancer chemotherapeutic agents. Moreover, TP is identical to platelet-derived endothelial cell growth factor (PD-ECGF), an angiogenic factor with anti-apoptotic properties. Increased expression of PD-ECGF/TP is found in many tumor and stromal cells, and elevated TP levels are associated with aggressive disease and/or poor prognosis. Thus, progression and metastasis of TP-expressing tumors might be abrogated by TP inhibitors that are used as single agents or in combination with (TP-sensitive) nucleoside analogues. On the other hand, increased TP activity in tumors may be exploited for the tumor-specific activation of fluoropyrimidine prodrugs, such as capecitabine. This review will focus on the different biological activities of PD-ECGF/TP and their implications for cancer progression and treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Disease Progression
  • Drug Delivery Systems / methods
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Models, Biological
  • Molecular Structure
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Neoplasms / prevention & control*
  • Thymidine Phosphorylase / antagonists & inhibitors*
  • Thymidine Phosphorylase / metabolism


  • Angiogenesis Inhibitors
  • Enzyme Inhibitors
  • Thymidine Phosphorylase