TGen, UA receive NFCR grant to study targeted pancreatic cancer therapies

The Translational Genomics Research Institute (TGen) and the University of Arizona (UA) have received a three-year, $600,000 grant to study targeted cancer therapies from the National Foundation for Cancer Research (NFCR).

The grant will enable TGen and the UA to continue its NFCR Center for Targeted Cancer Therapies (NCTCT), created in 2002, which is dedicated to discovering new therapies to treat pancreatic cancer, the nation's fourth leading cause of cancer death.

The Center is co-directed by TGen Physician-In-Chief Dr. Daniel Von Hoff, one of the nation's top oncologists and one of the world's leading authorities on pancreatic cancer, and by Dr. Laurence Hurley, a renowned medicinal chemist in the field of drug design and development and a Professor of Medicinal Chemistry and the Howard Schaeffer Endowed Chair in Pharmaceutical Sciences in the College of Pharmacy at UA.

"This NFCR grant should provide renewed hope for pancreatic cancer patients. This should help us move closer to better treatments and hopefully a cure for this devastating disease," said Dr. Von Hoff, who began working on the project when he was Director of the UA's Arizona Cancer Center in Tucson.

Researchers at NCTCT have developed new therapies that block the growth of pancreatic cancer cells by interfering with the molecules that promote pancreatic cancer cells, an approach called targeted cancer therapy.

"The overall objective of the research is to design and develop novel antitumor agents that will extend the productive lives of patients who have cancer," Dr. Hurley said. "Our medicinal chemistry research depends upon a structure-based approach to drug design that is intertwined with clinical oncology programs in cancer therapeutics directed by Dr. Von Hoff."

While traditional chemotherapeutic drugs impair cell division in a general way, targeted therapies specifically kill cancer cells and leave normal cells unharmed, resulting in enhanced cancer-killing power and fewer side effects.

"If we can create the right drug to turn on the right gene to turn off the cancer, that is going to be a whole new approach to treating this disease," said NFCR President Franklin C. Salisbury Jr. "This is 21st Century medicine. Not only do we need to support this research, but the world needs to know that we are on our way to curing cancer."

One specific area of research at NCTCT focuses on the development of agents that target the mutated K-Ras gene, which signals cancer cells to proliferate, migrate and survive.

"The NFCR grant is enabling us to go after a key gene that is the most common abnormal gene in pancreatic cancer. We want to target that gene," Dr. Von Hoff said.

Mutations in the K-Ras gene are found in more than 95 percent of pancreatic cancers. These mutations cause K-Ras proteins to be constantly activated. Inhibition of this mutant K-Ras gene should have profound effects on limiting the growth and survival of pancreatic cancer cells. Dr. Von Hoff and Dr. Hurley have identified promising compounds that, in laboratory tests, inhibit growth of pancreatic cancer cell lines expressing the mutant K-Ras gene. They hope to advance three new candidate compounds over the next three years.

Besides targeting the mutant K-Ras gene, the Center also is using computational methods to extract genomics and pathway information from cancer cells and match each patient with the most effective treatment option available.