Gene therapy for augmentation chemosentivities to anticancer drugs with improvement of therapeutic index

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Novel approaches are being investigated for improvement of therapies of human cancers. We have identified a strong association between sensitivity to 5-FU and levels of thymidine phosphorylase (TP) and thymidine kinase (TK) in either human gastric or colon cancer. In addition, after TP/PD-ECGF cDNA was successfully transfected into PC9 cells with use of a plasmid vector, the in vitro mechanism of augmentation of sensitivities to Doxifluridine and 5-FU was partly clarified, by use of the transfected cells, with obtaining confirmatory data of a bystander effect of a type of cell attachment included in the augmentation. A part of our research works, collaborating with the Department of Bacteriology I in Tokyo Jikeikai Medical College, firstly succeeded in yielding a retroviral vector involving TP/PD-ECGF cDNA and we are now conducting the investigation for further clarification of augmentation mechanism of chemosensitivities to Fluoro-pyrimidines. In the mean time, the level of TP enzyme, one of angiogenic peptides, is drastically decreased in both peritoneal seeding cells and in vitro cancer cells. Taken together, it can be considered that this newly developed retroviral vector involving TP/PD-ECGF cDNA may be substantially useful for study of tumor angiogenesis. Thus, the study of a virally directed enzyme prodrug therapy like this would have potential to propose invaluable methods for improvement of cancer chemotherapies.