Pancreatic cancer is one of the deadliest forms of cancer, with a five-year survival rate of only 13%.
It is known for being extremely resistant to treatment, making it very difficult to manage.
But researchers at the Indiana University School of Medicine have discovered a new way to weaken the disease by targeting two specific proteins that help cancer cells survive.
The study, recently published in Redox Biology, focused on a protein called redox effector factor-1 (Ref-1).
Scientists already knew that Ref-1 helps tumor cells resist treatment, but they found that another protein, peroxiredoxin-1 (PRDX1), makes Ref-1’s protective power even stronger.
Together, these two proteins create a shield that helps pancreatic cancer cells grow and fight off drugs.
To break through that shield, the team tested a new approach.
They used a drug they developed called APX2014 to block Ref-1, while also removing PRDX1.
The results were striking: when both proteins were shut down, tumors became much smaller and more cancer cells were destroyed compared to using the Ref-1 drug alone.
“What really surprised us was how important PRDX1 was in this process,” said Mark Kelley, Ph.D., the senior author of the study and professor of pediatric oncology research at IU.
“Out of the entire family of related proteins, only PRDX1 made tumors so much more sensitive to our Ref-1 drug. The combination worked far better than either treatment alone. In animal models, it even resulted in longer survival.”
The researchers also discovered that their treatment strategy didn’t just harm cancer cells. It also disrupted the environment around the tumor, which normally helps cancer survive. By interfering with both the cells and their support system, the treatment became even more effective.
The work was carried out by scientists at the Herman B Wells Center for Pediatric Research and the IU Melvin and Bren Simon Comprehensive Cancer Center.
Their next step is to continue developing drugs that target PRDX1, while also improving Ref-1 inhibitors like APX2014. They hope to test these drug combinations in other cancers and eventually move toward clinical trials in humans.
“This research shows us a brand new vulnerability in pancreatic cancer,” said Melissa Fishel, Ph.D., co-author of the study and associate professor of pediatrics and pharmacology at IU.
“By hitting both Ref-1 and PRDX1 together, we may be able to shut down the survival systems that make these tumors so difficult to treat.
This could lead to combination therapies that work better than anything we have today—not just for pancreatic cancer, but possibly for other aggressive cancers as well.”
