Radiation therapy as a pound of prevention? A ray of hope for pancreatic cancer patients

Dr. Sana Karam, PhD

Wings of Hope for Pancreatic Cancer Research funds work at Anschutz Medical Campus

By Peter Jones

Using radiation to kill malignant cells in the body is nothing new, but thanks in part to funding from Wings of Hope for Pancreatic Cancer Research, oncologists are continuing to explore newer applications for one of their more standard medical therapies.

Highly targeted radiation is increasingly seen as more of a strategic medicine than simply an all-out assault on cancer cells, according to Dr. Sana Karam, a radiation oncologist at the University of Colorado’s Anschutz Medical Campus in Aurora.

“I think we have to migrate away from just a cancer-cell kill [scenario],” she said. “You have to think of pancreatic cancer as a big tumor with an environment around it. I’m using the radiation to trigger an immune response.”

Pancreatic cancer has historically been one of the most aggressive and difficult-to-treat malignancies. Even when patients have been subject to aggressive radiation therapies, the stubborn cancer cells have often regrown within months. To hear Karam tell it, the pancreas is an organ practically made for these kinds of medical challenges.

“It has a lot of scar tissue to begin with,” she explained. “It has a lot of immunosuppressive cells that the good immune cells cannot penetrate. The bad immune cells are living there and loving it. To get a drug in there is like trying to drill a hose into a stone.”

To meet the challenge, Karam has turned her attention to a brand of radiation therapy that has slowly become common in treating lung and skin cancers, and she is guardedly hopeful that the remedy will be just as effective inside the obstinate pancreas. Karam describes the therapy as less a frontal assault on cancer than a preventative vaccine against the recurring cancer cells.

“We’re able to track movement, so we can deliver a high dose to a very small region with neighboring structures that are very sensitive to radiation, like the heart” the researcher said. “The traditional ways of treating pancreatic cancer with radiation have failed.”

In Karam’s animal studies, many of the mice injected with pancreatic cancer cells lived more than five times longer than those receiving no therapy. In the later human safety trials, the targeted radiation was well tolerated in 18 patients, regardless of doses.

“We saw a very nice invigoration of the immune response, which is a great thing,” Karam said, stressing that the trial was only designed to test safety. “What we know is that it is safe, but it was not powered enough for efficacy. But speaking anecdotally, it did very well.”

How and why the therapy works as a vaccine remains an open question. Karam suspects the radiation may be sounding a sort of emergency alarm on the cancer cells, garnering the attention of the cancer-fighting T cells that are supposed to fend off the disease, but struggle in the pancreas.

“It’s a new area, so I don’t think anyone knows the answer with 100% certainty,” Karam said. “But the idea is that when you kill cancer cells or anything in the vicinity, you unmask the cancer cells to the T cells, which before were not seeing the cancer cells.”

Those mechanics are why the radiation therapy should come before any immunotherapy treatments on a patient’s pancreas, according to Karam.

“It makes no sense to give immunotherapy before the radiation. There’s no signal for that immunotherapy to work,” she said. “You want to give it afterwards when the signal is heightened.”

Although much research must be conducted before any final conclusions can be made, Karam is cautiously optimistic about the therapy’s long-term benefits for pancreatic cancer and beyond.

“It’s really exciting,” she said. “With the right therapies, radiation has the potential to activate the immune system everywhere throughout the body.”

Seed money for Karam’s research came from Wings of Hope for Pancreatic Cancer Research, an organization founded by former Castle Pines Mayor Maureen Shul in 2012 after losing two of her family members to the disease. The funding came from one of three $50,000 grants awarded in 2019 by Wings of Hope to fund pancreatic cancer research at the CU Cancer Center.

For more information on Wings of Hope, visit wingsofhopepcr.org.