Strategies in Gene Therapy
Gene therapy is the ability to replace abnormal or mutated genes with the normal copy of the gene to inhibit ongoing tumor cell growth. We are currently studying two tumor suppressor genes which have been successfully incorporated into a stable form for delivery directly into human pancreatic tumors. Most genes are delivered to human tumors in a virus particle which allows their stable incorporation into the DNA of the tumor. Our current studies are underway in mice and will soon be ready for study in human investigational trials.
Selected References
Bouvet M, Bold RJ, Lee J, Evans DB, Abbruzzese JL, Chiao PJ, McConkey DJ, Chandra J, Chada S, Fang B, Roth JA. Adenovirus-mediated wild-type p53 tumor suppressor gene therapy induces apoptosis and suppresses growth of human pancreatic cancer. Ann Surg Oncol 1998; 5:681-688.
Grau AM, Zhang L, Wang W, Ruan S, Evans DB, Abbruzzese JL, Zhang W, Chiao PJ. Induction of p21wafl expression and growth inhibition by transforming growth factor-B involve the tumor suppressor gene DPC4 in human pancreatic adenocarcinoma cells. Cancer Res 1997;57:3929-3934.
Pearson AS, Bouvet M, Evans, DB, Roth JA. Gene therapy and pancreatic cancer. Frontiers in Bioscience 1998;3:e230-237.
Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary K, Chiao PJ. The NF-kB transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. In press: Clin Cancer Res.