By Wendy Sarubbi | October 1, 2012 12:38 pm

Two College of Medicine researchers have been awarded a grant to develop a combination therapy that for the first time uses a polyamine transport inhibitor (PTI) to prevent chemotherapy resistance by pancreatic cancer cells.

The College of Medicine’s Dr. Otto Phanstiel and Dr. Deborah Altomare will use the $289,000 grant from the US Army Medical Research and Materials Committee to target pancreatic cancer, the fourth leading cause of cancer deaths in the United States.

The project will use a PTI in combination with a chemotherapy drug, difluoromethylornithine (DFMO), which inhibits polyamine biosynthesis. The idea is to suppress the levels of intracellular polyamines, which are compounds that help tumors grow.

“DFMO blocks the polyamine factory inside cells, while the PTI blocks polyamines outside the cell from entering into the cell,” said Dr. Phanstiel.

Dr. Phanstiel and Dr. Altomare hope to show the combination therapy will result in sustained polyamine depletion within cancer cells, thereby starving the cell of these key growth factors and triggering cell death.

“We will look at how mice will tolerate the combination therapy, and how this treatment affects the tumor and normal tissues,” said Dr. Altomare. “Are the mice losing weight? Are they lethargic? Et cetera.”

DFMO by itself has been used for over 40 years in treatment, Dr. Phanstiel said, but cancer cells can escape the DFMO-only therapy by importing polyamines from outside the cell. As the drug’s effectiveness fades, cancer cells can recover and continue to grow. The combination approach (DFMO+PTI) should block this escape pathway.

There are many forms of pancreatic cancer. Current treatments are surgery, radiation therapy and chemotherapy. However, the outlook for patients remains grim, because the disease spreads rapidly and is seldom detected in its early stages because the symptoms are so vague.

“We hope the lessons learned in this project will teach us which pancreatic tumors will be most sensitive to this new therapy,” Dr. Phanstiel said.



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