Enzyme-Prodrug Systems: Thymidine Phosphorylase/5-Deoxy-5-Fluorouridine

Thymidine phosphorylase (E.C. 2.4.2.4) (TP), also described as the angiogenic platelet-derived endothelial cell growth factor (PD-ECGF) (1 –4 ), is a homodimeric enzyme with a monomeric molecular mass of about 55 kDa (5 ,6 ) that phosphorolytically cleaves thymidine to yield thymine and deoxyribose-1-phosphate (dR-1-P) (7 ,8 ). TP is expressed in various human cells and tissues and plays a role in plasma thymidine homeostasis (9 –11 ). The levels of expression in different human tissues can vary up to 15-fold (12 ). Moreover, TP levels are increased in several types of malignant tumors when compared to the non-neoplastic regions of these tissues (13 ) and also in the plasma from tumor-bearing animals and cancer patients (14 ).