Thymidine phosphorylase (platelet-derived endothelial cell growth factor) as a target for capecitabine: from biology to the bedside.
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.
Ranieri
Girolamo
G
National Cancer Institute, Interventional Radiology Unit, Bari, Italy.
Roccaro
Aldo Maria
AM
Vacca
Angelo
A
Ribatti
Domenico
D
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010330:Patents as Topic; D011878:Radiotherapy / Q000009:adverse effects; D012039:Regional Blood Flow; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil