Targeting platelet-derived endothelial cell growth factor/thymidine phosphorylase for cancer therapy.
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.
Liekens
Sandra
S
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. sandra.liekens@rega.kuleuven.be
Bronckaers
Annelies
A
Pérez-Pérez
Maria-Jésus
MJ
Balzarini
Jan
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D013939:Thymidine Phosphorylase