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

Abstract

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.

• Authors: Sandra Liekens, Annelies Bronckaers, Maria-Jésus Pérez-Pérez, Jan Balzarini
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 74 Issue 11 Pg. 1555-67 (Dec 03 2007) ISSN: 0006-2952 [Print] England
• PMID: 17572389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Angiogenesis Inhibitors
• Enzyme Inhibitors
• Thymidine Phosphorylase

Topics

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