Two well-established gene-directed enzyme prodrug therapy strategies, in which Herpes simplex virus 1-thymidine kinase (HSV1-TK) or cytosine deaminase (CD) was used in combination with prodrug ganciclovir (GCV) or 5-fluorocytosine (5-FC) respectively, have been proposed for hypoxia-driven gene therapy in different tumor models (9,10). Here, TKT is linked to neoplasm.