Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells

New 'suicide gene' delivery approach offers potential for novel therapy

PHILADELPHIA – A research team, led by investigators at the Department of Surgery at Jefferson Medical College of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, has achieved a substantial "kill" of pancreatic cancer cells by using nanoparticles to successfully deliver a deadly diphtheria toxin gene. The findings – set to be published in the October issue of Cancer Biology & Therapy – reflect the first time this unique strategy has been tested in pancreatic cancer cells, and the success seen offers promise for future pre-clinical animal studies, and possibly, a new clinical approach.

The researchers found that delivery of a diphtheria toxin gene inhibited a basic function of pancreatic tumor cells by over 95 percent, resulting in significant cell death of pancreatic cancer cells six days after a single treatment. They also demonstrated that the treatment targets only pancreatic cancer cells and leaves normal cells alone, thus providing a potential 'therapeutic window.' Further, they are targeting a molecule that is found in over three-quarters of pancreatic cancer patients.

"For the pancreatic cancer world, this is very exciting," says the study's lead author, molecular biologist Jonathan Brody, Ph.D., assistant professor, Department of Surgery at Jefferson Medical College of Thomas Jefferson University, who works closely with the Samuel D. Gross Professor and Surgeon, Charles J. Yeo, M.D. "There are no effective targeted treatments for pancreatic cancer, aside from surgery for which only a minority of patients qualify. We are in great need of translating the plethora of molecular information we know about this disease to novel therapeutic ideas."

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the U.S., reflecting the generally short survival time of patients - often less than a year from diagnosis.

This approach was originally developed in ovarian cancer cells by study co-author Janet Sawicki, Ph.D., a member of the Kimmel Cancer Center, and professor at the Lankenau Institute for Medical Research in Wynnewood, Pennsylvania. She and her group had recent success in reducing the size of ovarian tumors following treatment with diphtheria toxin nanoparticles.