Der lab finds promising drug to fight pancreatic cancer

In the lab of Channing Der, PhD, a UNC Lineberger member and a Kenan Distinguished Professor in the Department of Pharmacology, researchers believe they have found a promising strategy to target a type of pancreatic cancer that is notoriously resistant to treatment—pancreatic cancer that has a mutation in a gene called KRAS.

Der lab finds promising drug to fight pancreatic cancer click to enlarge Channing Der, PhD
Der lab finds promising drug to fight pancreatic cancer click to enlarge Andy Boyette

Just five months after receiving an unexpected diagnosis of pancreatic cancer, Andy Boyette gathered 88 of his family members and friends for a “celebration of life” party in Raleigh, complete with barbecue and balloons.

Diagnosed with stage IV pancreatic cancer that had spread to his liver, Boyette was told he might have just 12 months to live. Pancreatic cancer is a particularly aggressive and deadly cancer, with just seven percent of patients surviving after five years. At his party, Boyette tried to talk with each of his loved ones, thinking it could be the last time.

Ironically, it’s been nearly three years since Boyette, now 64, received his diagnosis. He’s considered to be a walking miracle by his family, and he has big plans for the future.

“There are so many things I want to see and do, and that my children are going to do, and I don’t want to miss those,” Boyette says. If his health is good, he wants to take a cross-country motorcycle trip to San Francisco so he can eat all the lobster he wants. And as a father of four, Boyette recently had the opportunity to watch one of his daughters graduate with honors from N.C. State University. He expects to see his youngest graduate in May. At nearly every visit to his doctor at the N.C. Cancer Hospital, he shares his dream of walking his girls down the aisle. 

“I want to give them away,” he says. “I want to be there in spirit and in body.”

To help improve the outlook for patients like Boyette, researchers at the UNC Lineberger Comprehensive Cancer Center are working to find new treatments for pancreatic cancer. 

In the lab of Channing Der, PhD, a UNC Lineberger member and a Kenan Distinguished Professor in the Department of Pharmacology, researchers believe they have found a promising strategy to target a type of pancreatic cancer that is notoriously resistant to treatment—pancreatic cancer that has a mutation in a gene called KRAS.

Their strategy, published in the journal Cancer Cell, is to use a drug designed to target the last of a series of signals that drive abnormal growth in KRAS-mutated cancer cells. The RAF-MEK-ERK pathway becomes aberrantly activated in cancers with KRAS mutations, Der said. In preclinical studies in cells and in mice, they tested an investigational drug that blocks the protein ERK. 

Researchers found that nearly 50 percent of the human pancreatic cancer cell lines they tested responded to the drug. The drug also had a significant effect on tumor growth in animal models. They believe their findings pave the way for clinical trials; however, their work is not done.

“We don’t think that an ERK inhibitor is just the miracle drug and we’re done,” Der explains. “We believe these cancers will figure out a way to develop resistance. And we believe that while these ERK inhibitors may be better than existing drugs targeting this pathway in this particular cancer, to really activate a successful long-term response in the patient, we’re going to have to identify another inhibitor that will work in combination with the ERK inhibitor to overcome resistance.”

Finding new pancreatic cancer treatments is a personal mission for scientists working in Der’s lab, including Kirsten Bryant, PhD, a postdoctoral fellow at UNC Lineberger. 

Bryant began researching cancer as an undergraduate, but she really saw the need for more work in pancreatic cancer when her dad was diagnosed with the disease during her final year of graduate school. Although her father knew the odds were stacked against him, he didn’t give up his fight against the disease, Bryant said. He was treated with two chemotherapy regimens, but his tumor developed resistance, and there were significant side effects. He died just 11 months later. 

Kirsten Bryant, PhD
 

“Watching his battle with this disease really instilled in me the need for more research on this particular cancer,” Bryant says. “I am passionate about continuing my dad’s fight, and I sincerely hope that my work will one day lead to better treatment options for patients.”

Boyette’s doctor, Autumn McRee, MD, a UNC Lineberger member and assistant professor in the UNC School of Medicine, agrees that new treatments for pancreatic cancer are urgently needed. It has been an honor to watch Boyette live a full and productive life while enduring cancer and its treatment, she says. He started on an aggressive chemotherapy regimen with an emphasis on improving his survival, but also preserving his quality of life. Boyette’s cancer continues to respond to the treatment. 

“Andy, however, is the exception to the rule, and while the results of sequencing of his tumor may provide insight into his positive response to chemotherapy, many patients with pancreatic cancer only respond to chemotherapy for short periods of time. Therefore, more effective therapies are urgently needed with less toxicity and improved durations of response,” says McRee. 

Boyette also wants to see more research dollars go to attacking pancreatic cancer, as well as increased awareness about the disease, which is the fourth leading cause of cancer death in the United States.

“It’s killing a lot of people—men and women,” he says. “I’m one of the lucky ones.”

Personally, he finds strength in his doctors at UNC, in his former wife Pattie Moore-Boyette, and his church. He distracts his mind with baking, and with working when he can. But he gives most of the credit to God as well as to his body and his mind, which have sustained three years of treatment.

He said the night before he started his first chemotherapy treatment, he decided to have a positive mindset and attitude so that the next day would be a pleasant experience. He emphasizes the power of the mind in coping with cancer.

“My body is fighting the cancer, and I’ve also got to control it up here,” he said, pointing to his head. “Your mind is very powerful, and you can’t let it take over.”