Thymidine phosphorylase (platelet-derived endothelial cell growth factor) as a target for capecitabine: from biology to the bedside.

Abstract	Thymidine phosphorylase (TP), also known as platelet derived endothelial cell growth factor (PD-ECGF), is an enzyme involved in thymidine synthesis and degradation and exerts an angiogenic activity, whereas N4 pentyloxy-carbonyl- 5'-deoxy-5-fluorocytidine, commonly called capecitabine (CAP), is a TP-activated oral fluorpyrimidine, which generates 5-fluorouracil (5-FU) within tumours. In addition to its classic antitumour activity, recent studies suggest that CAP may act as an antiangiogenetic molecule. Assessment of tumour microvessel density as expressed by endothelial cell TP positivity may identify the most vascularized and hence CAP-sensitive tumours. This review summarizes: (i) the biochemical and tissue expression of TP; (ii) the pharmacological profile of CAP as an anti-cancer compound and the central role of TP in its activation; (iii) the potential antiangiogenetic role of TP-activated CAP in tumours.
Authors	Girolamo Ranieri, Aldo Maria Roccaro, Angelo Vacca, Domenico Ribatti
Journal	Recent patents on anti-cancer drug discovery (Recent Pat Anticancer Drug Discov) Vol. 1 Issue 2 Pg. 171-83 (Jun 2006) ISSN: 1574-8928 [Print] United Arab Emirates
PMID	18221035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References	Angiogenesis Inhibitors Antimetabolites, Antineoplastic Deoxycytidine Capecitabine Thymidine Phosphorylase Fluorouracil
Topics	Angiogenesis Inhibitors (pharmacology, therapeutic use) Animals Antimetabolites, Antineoplastic (pharmacology, therapeutic use) Capecitabine Clinical Trials as Topic Deoxycytidine (analogs & derivatives, pharmacology, therapeutic use) Fluorouracil (analogs & derivatives, pharmacology, therapeutic use) Humans Neoplasms (blood supply, drug therapy) Neovascularization, Pathologic (drug therapy) Patents as Topic Radiotherapy (adverse effects) Regional Blood Flow Thymidine Phosphorylase (antagonists & inhibitors, biosynthesis) Up-Regulation (drug effects, radiation effects)

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