IU School of Medicine helps discover new vulnerability in pancreatic cancer

INDIANAPOLIS (WISH)– Scientists at the Indiana University School of Medicine have helped to discover a new way to undermine pancreatic cancer’s defenses by blocking two key proteins that help the disease resist treatment.

The study, published in October 2025 edition of Redox Biology, found that combining drugs to block redox effector factor-1 (Ref-1) and peroxiredoxin-1 (PRDX1) could shrink tumors and increase cancer cell death more effectively than either treatment alone.

Pancreatic cancer, with a five-year survival rate of just 13%, is one of the most treatment-resistant cancers. Researchers developed a drug, APX2014, to inhibit Ref-1 and paired it with removal of PRDX1. The combination disrupted tumor survival systems, leading to smaller tumors and longer survival in animal models.

Mark R. Kelley, a corresponding author of the study and the med school’s Betty and Earl Herr Professor of Pediatric Oncology Research, said, “What really surprised us was how specific PRDX1 was in driving this effect. The combination worked better than either treatment alone, and in animal models, it resulted in smaller tumors and longer survival.”

The findings also showed that the approach affected both tumor cells and their surrounding environment, a factor researchers say is critical for weakening cancer’s resilience.

Melissa L. Fishel, PhD, a co-author of the study and an associate professor at the med school, said, “This research shows us a brand new vulnerability in pancreatic cancer. By targeting both Ref-1 and PRDX1 together, we may be able to shut down the survival systems that make these tumors so hard to treat.”

The research team, which included scientists from IU’s Herman B Wells Center for Pediatric Research and the IU Melvin and Bren Simon Comprehensive Cancer Center, plans to continue developing drugs that target PRDX1 alongside Ref-1 inhibitors. They also hope to expand the work to other aggressive cancers and move closer to clinical trials.

The National Institutes of Health and the Riley Children’s Foundation supported the study.

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