University of Colorado Cancer Center member Sana Karam, MD, PhD, has received a translational research grant from the V Foundation for Cancer Research, co-founded by ESPN and legendary basketball coach Jim Valvano, to study a new therapeutic that may help pancreatic cancer patients overcome resistance to radiation therapy.
“Pancreatic cancer is deadly. The only treatment that can cure it is surgery to fully remove the tumor, but that is only an option when the cancer is caught early, which is rare,” Karam explains. “Radiation alone to shrink tumors before surgery has been tried, but with limited benefit. By studying patient and animal models, we discovered that while radiation can kill cancer cells and stimulate some good immune cells, it also can make the environment harsh, help cancer cells escape, and bring in some bad immune cells. It can also scar the tumor, making surgery harder.”
This project has earned Karam the Bob Bast Translational Research Grant, awarded to the V Foundation adult translational research project that received the highest ratings in 2023. Bob Bast, MD, chaired the V Foundation’s Scientific Advisory Committee for more than 20 years and continues to serve on the SAC and V Foundation board.
How STAT3 contributes
In her V Foundation-funded study, Karam plans to further study the role of a molecule called STAT3 that enables the negative effects of radiation. In a previous research project, Karam and her team found that blocking STAT3 preserved the benefits of radiation therapy while hindering the undesired consequences. In her new study, Karam will test a pill patients can take, while undergoing radiation, that blocks STAT3.
>> For more information on the clinical trial, visit the CU Anschutz Medical Campus' clinical trials page.
“In liver cancer, this drug was quite effective, and the FDA has prioritized it for trials,” Karam says. “This is the first time it will be combined with radiation to treat pancreatic cancer in humans. We will collect blood and tissue from pancreatic cancer patients before and after the pill-and-radiation treatment and study how this combination affects the tumor and the patient’s immune system. We also hope to develop a test that predicts patient response to combination of radiation and the STAT3 blocker and to identify other ways the cancer cells might be escaping.”
Patient benefits
A successful trial, Karam says, would mean reduced morbidity and mortality for pancreatic cancer patients, making surgery a possibility, especially less complicated surgery to remove tumors that have been successfully reduced in size by radiation.
“I anticipate good outcomes, based on what we’ve seen and how this drug is performing in cancers that are similar to pancreatic cancer,” she says. “But even for those who may not respond, understanding the biology around response and resistance will be highly significant for developing future therapies. The current 10% five-year survival rate for this cancer is not acceptable.”
A long road
Karam’s research into radiation resistance in pancreatic cancer has been a yearslong journey, and she emphasizes that it’s not one she has taken alone. CU Cancer Center Director Richard Schulick, MD, MBA, and CU Cancer Center member, Marco Del Chiaro, MD, clinical director of the hepato-pancreato-biliary program in the CU Department of Surgery, and the entire medical oncology team, have been with her every step of the way, she says, and she is grateful for their support.
She is also grateful to the V Foundation, as well as Wings of Hope, for the funding that may have lifesaving results for future pancreatic cancer patients.
“It’s an incredible honor to be recognized by people who are so passionate about cancer research,” she says. “It’s funded by patients, by families, by those who have walked that journey. I take that as a badge of honor, and I will make sure that we live up to that name.”
