New MUSC grant fuels research to crack genetic code on deadly cancer

Compliments of Post and Courier

A sharp pain in the gut doesn’t sound like a blessing, but for Rob Hessler it was.

“It felt like somebody was stabbing me in the stomach with a knife,” said Hessler, 75, of Johns Island.

That pain turned out to be a very early stage pancreatic tumor, a cancer that rarely has acute symptoms and is usually found only after it has spread to other organs. It is one reason pancreatic cancer has such dismal outcomes: only 11 percent of patients live five years after diagnosis. Many don’t make it a year.

But a grassroots nonprofit group fueling more research into pancreatic cancer has taken hold in South Carolina, and it resulted in a new grant pushing promising research at Hollings Cancer Center at Medical University of South Carolina. The Pancreatic Cancer Action Network (PanCAN) awarded $10.5 million in new research grants nationally, including $250,000 in a Career Development Award to Dr. Aaron Hobbs at MUSC for his work looking at a peculiar mutation in some pancreatic tumors that could become a biomarker and a potential target for therapy, a first for South Carolina.

Dr. Aaron Hobbs, an assistant professor in the Department of Cell and Molecular Pharmacology at Hollings Cancer Center at Medical University of South Carolina, was recently awarded a $250,000 Career Development Award from the Pancreatic Cancer Action Network. He is looking at specific mutations in pancreatic cancer that could be biomarkers or provide targets for new therapies. MUSC Hollings Cancer Center/Provided

Part of the reason pancreatic cancer has such a poor prognosis is there are no screening exams for it and symptoms don’t usually show up until the cancer is well advanced, said Dr. Denis Guttridge, associate director of translational science for Hollings and director of the Darby Children’s Research Institute at MUSC.

“You come in, you feel a little jaundiced, or you don’t feel right. And you are already at Stage IV,” with cancer spread to other organs, he said. “That happens to 80 percent of the patients. And they have one year to live. So that is really frustrating.”

To make matters worse, pancreatic cancer is often accompanied by a severe wasting syndrome called cachexia that strips the patients of flesh and muscle.

“Even 70 percent of patients that are in the early stages will undergo this kind of wasting syndrome,” Guttridge said. “It’s very difficult for the physicians to treat when they know the patients are already losing weight and muscle mass.” That might lead them to give smaller doses of drugs than necessary, which could weaken the effectiveness of their treatment, he said.

It is also tough on the families, Hobbs said.

“Not only watching a loved one pass away but watching them waste away, from who they were to being emaciated, is painful for everybody,” he said.

A well-known inflammatory factor may be involved in both the cancer and wasting, said Guttridge, who studies the factor called Nuclear Factor kappa B, or NF-kappaB. In pancreatic cancer in animal models, by blocking the inflammatory factor “you have a very nice response,” Guttridge said. It also appears to be driving the muscle-wasting in the body, he said. That would make it a good target for therapy “because then we would be able to treat both the cachexia and the cancer,” Guttridge said.

Immunotherapy is leading to improvements in many previously difficult to treat cancers, including advanced melanoma, cervical cancer and lung cancer. It’s driven by the discoveries of key mutations in those cancers that could then be targeted with more precise therapies that work in concert with the immune system.

That hasn’t happened yet for prostate cancer, although there are reasons to hope it would be possible, researchers said. A gene called KRAS is mutated in many cancers but in nearly all or 95 percent of pancreatic ductal adenocarcinomas, which make up the vast majority of pancreatic cancers.

It is one reason the nonprofit was interested in Hobbs’ work.

“We are grateful to Dr. Hobbs and his team’s commitment to studying pancreatic cancer biology and are hopeful their studies will lead to a better understanding of KRAS, which is mutated in nearly all pancreatic tumors,” said Julie Fleshman, president and CEO of PanCAN. “The grant awarded to his lab at MUSC is part of PanCAN’s largest-ever single year research investment and was made through a competitive, peer-review process. Innovative projects like these will advance the field, allowing us to better understand how the disease develops and progresses, develop more effective treatments and identify new strategies to diagnose it earlier.”

Even with that knowledge, it has been difficult to find therapies that would exploit that. Hobbs is studying a particular form of that mutation, which is found in about 15-20 percent of pancreatic cancers but in few other cancer patients. 

It points toward a way the pancreatic cancer cells fuel themselves and survive. Those cells can gulp in proteins, nutrients and other elements floating outside the cell.

“You can think of it as a cellular binge-drinking,” Hobbs said.

They can then break down and reshape those materials into what they need to survive, he said. But in cancer cells with this particular mutation, dubbed G12R, that process doesn’t happen the normal way, yet the cancer cells still seem to pull in the materials and reshape them into what it needs. Part of it may be the cell using a similar process, a kind of recycling program, that has been effectively targeted and blocked by drugs commonly used to treat other things, such as malaria.

Not only does it open the door for therapy for some patients but the mutation itself could serve as an important biomarker that could, for instance, tell oncologists which patients might respond better to some therapies, Hobbs said. That is an important goal of the PanCAN grants and network, he said.

“We know right now this is not an easy battle, but we want to try to give each person their best shot at it,” Hobbs said. “People do survive. And that has been in part from their efforts and all of our efforts, the whole research field.”

Hessler could be the outcome researchers and advocates would like to see for all pancreatic cancer patients. Because his cancer was found so early, he was able to start chemotherapy right away and, other than losing his hair, did not suffer some of the extreme side effects others have to endure. He and his wife, Bonnie, were splitting time between Cape Cod and Johns Island then, and he would get chemo up north and then head out for Charleston.

“Psychologically, it was a wonderful way to get away from the medical environment of being in a hospital,” Hessler said, until he had to go back for more. 

“I never stopped leading a normal life,” he said. “I could basically do whatever I wanted to do.”

But he balked at getting a Whipple procedure, a surgery that would remove the cancer and part of the pancreas, small intestine and other affected organs, including a third of his stomach. Then he talked to Dr. David Mahvi, director of the Division of Surgical Oncology at MUSC. 

“He said, ‘If you don’t do it, you’ll be dead in six months,’” Hessler said. “So I said, ‘Alright, let’s talk Whipple surgery.’” 

He can laugh about that now. The outcomes were so good that Hessler was a guest speaker when PanCAN launched a chapter in South Carolina last year. He has since gotten to know Hobbs and Guttridge and is helping to fund some of their work. He would like to see them come up with something that is better than the current chemotherapy that is so hard on some patients.

“If they can find a way to get around that or minimize it, that is a big step in the right direction,” Hessler said. “Anything I can do to help them, I will.”

Meanwhile, he gets scans every six months to see if his cancer has returned. Otherwise, he is defying the disease by eating what he wants and golfing when he can. The perception is slowly changing as progress is made, Hessler said.

“There is a much greater awareness that it is not a death sentence,” he said. “To get pancreatic cancer is not the end of the world.”

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