“This gene is important in the progression of pancreatic, lung, colorectal and other cancers,” said Tracy Brooks, assistant professor of pharmacology and the grant’s primary investigator. “We are focusing on the region of DNA that controls how much kRAS gets produced, with the ultimate goal of using the knowledge gained in a targeted drug-discovery program to develop new agents with better safety and efficacy against many cancers.”
The grant was awarded through the Peer Reviewed Cancer Research Program, DOD’s highly competitive new funding mechanism. Only about 16 percent of applications submitted to PRCRP were selected for funding this year, and only three grant applications focusing on pancreatic cancer were funded.
Brooks’ study focuses on alternative DNA structures, particularly one called the G-quadruplex, or G4, which is formed in guanine-rich DNA.
“When formed in regions of DNA that control proteins, called promoters, they tend to turn off protein production,” she said. “In the case of kRAS, turning the gene off can kill the pancreatic cancer cells. Our work is aimed at figuring out the major ‘shape’ of the G4 that forms within the kRAS promoter region and how it is controlled by other proteins in the cell.”
With that information, Brooks hopes to work with molecular modelists to determine the structure’s 3-D shape, so she and others can predict potential chemicals to strengthen the structure.
Brooks can then work with pharmacognosists and medicinal chemists to identify and create new chemicals and drugs that will stabilize the G4 structure, turn off the kRAS gene and selectively kill pancreatic, lung and colorectal cancers in combination with traditional chemotherapeutic agents.
“Dr. Brooks’ research on the gene kRAS has the potential to unlock a novel mechanism in the control of many types of cancers,” said Stephen Cutler, chair of the Department of BioMolecular Sciences, of which Brooks is a part. “The potential impact of her studies on managing neoplastic disorders is extremely high. We are fortunate to have her as one of our School of Pharmacy faculty members.”
For Brooks, the study is highly personal.
“When I was a freshman in college, after only about a one-week battle, my grandmother died from pancreatic cancer,” she said. “It is one of the deadliest cancer diagnoses and one in dire need of new therapy options.
“Since her passing, I’ve lost cousins, friends, my mother and my husband’s grandfather to cancer, and I was a caretaker for my husband during his battle with cancer when he was only 36. Thankfully, he is a three-year cancer survivor, but it was an arduous battle. I’ve dedicated my career, and my life, to researching and combating this disease.”