Development of antisense therapy for pancreatic cancer or hepatoma : potential of the tumor targeting.

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I have sought the potential of the tumor targeting to achieve successful gene the rapy for pancreatic cancer or hepatoma including antisense therapy.1. Studies concerning K-ras, DPC4, p53 and cyclin A in pancreatic cancer and the inhibitory effect of caffein on hepatocarcinogenesis have been performed, and the results have been published or are in press. It seems to be worthy to design a strategy of gene therapy for pancreatic cancer or hepatoma by targeting the ras signalling pathway.2. A novel tumor-targeting peptide vector (cRGD-hK) has been developed, that is intended to be systemically and repeatedly administered to patients with advanced solid tumors (the patent application has been done). The peptide vector of 36 1-amino acid residues, CRGDCF (K[H-]KKK) 6, has three elements : (i) a tumor-homing RGD motif to target tumor tissues, (ii) cationic oligolysine to form complexes with plasmid DNA or oligonucleotides, and (iii) histidyl residues to facilitate the escape from the acidic endosomes. Using CMV-driven luciferase expression plasmids as a reporter in pancreatic cancer and hepatoma celllines, the potential usefulness as a tumor-targeting vector was demonstrated in vitro and in vivo. The results were presented at the 3rd Conference of American Society of Gene Theraphy and at the 9th International Conference of Cancer Gene Therapy. Even if the targeting of cancer cells is successful, it seems to be unrealistic to expect a transduction of the majority of cells. In addition to repetitive antisense theraphy, we propose a potential non-viral gene theraphy for advanced pancreatic cancer or hepatoma through use of the tumor-targeting peptide vector and the concept of RNA interference.