New Dual Protein Target Strategy Shows Promise Against Pancreatic Cancer

Researchers at Indiana University School of Medicine have discovered a promising new approach to weaken the defenses of pancreatic cancer by simultaneously targeting two critical proteins that enable the disease to resist treatment. Published in the journal Redox Biology, the study demonstrates that combining drugs to inhibit both proteins—redox effector factor-1 (Ref-1) and peroxiredoxin-1 (PRDX1)—can substantially reduce tumor growth and improve cancer cell death.

Pancreatic cancer remains one of the deadliest cancers, with a five-year survival rate of only 13%, largely due to its resistance to conventional therapies. The study focused on Ref-1, a protein that helps tumor cells survive under stress, and found that PRDX1 further enhances its protective effects. When researchers used a drug called APX2014 to block Ref-1 and simultaneously suppressed PRDX1, tumors shrank significantly and more cancer cells underwent apoptosis.

Lead researcher Mark Kelley, Ph.D., explained that the specificity of PRDX1 in driving tumor resistance was surprising yet crucial. Loss of PRDX1 made tumors much more sensitive to Ref-1 inhibition, leading to better outcomes in animal models. The approach not only affected the tumor cells but also impacted their surrounding environment, disrupting the support systems that promote tumor survival.

Looking forward, the research team from the Herman B Wells Center and IU Melvin and Bren Simon Comprehensive Cancer Center plans to further develop drugs targeting PRDX1 in combination with existing Ref-1 inhibitors. They aim to explore the potential of this strategy in other aggressive cancers and move closer to clinical trials.

According to co-author Melissa L. Fishel, Ph.D., this dual-targeting approach unveils a new vulnerability in pancreatic cancer, paving the way for more effective combination therapies that could surpass current treatments and help save lives. Researchers continue to investigate how this method might be applied broadly across different cancer types, offering hope for more durable and effective therapies in the future.

For more detailed findings, refer to the publication: Sonia Kiran et al, "The absence of Peroxiredoxin-1 in human pancreatic ductal adenocarcinoma (PDAC) markedly reduces cell survival and tumor growth when coupled with the inhibition of Ref-1 redox signaling," Redox Biology (2025).