News — Chicago (April 15, 2025) — Despite significant progress in cancer research, pancreatic ductal adenocarcinoma — the most prevalent and challenging form of pancreatic cancer — remains difficult to treat. However, a new combination therapy could help change the trajectory of this cancer, with a preliminary animal study showing its potential to target the disease more effectively.
In a new study, researchers found that combining a drug that blocks the activity of the epigenetic protein PRMT5 with a drug that inhibits the Chk1 DNA repair protein produced synergistic effects against pancreatic tumor growth in mice.
“Pancreatic cancer is the third leading cause of cancer-related deaths in the United States and is projected to become the second by 2030,” the study’s first author Madeline Dzikowski, a doctoral student at the Medical College of Wisconsin. “Large-scale studies have shown that PRMT5 is overproduced in pancreatic cancer patients and that higher levels are linked to shorter overall survival, making PRMT a promising target for developing new therapies.”
Dzikowski will present the research at the , which is being held April 12–15 in Chicago.
The epigenome is a set of chemical modifications to DNA and histone proteins that regulate gene expression without changing the genetic sequence. PRMT5 helps directly regulate the epigenome by controlling DNA organization and protein access, making it essential for many cellular functions. In cancerous cells, the epigenetic mechanisms controlled by PRMT5 are hijacked in a way that leads to unchecked activity.
“Epigenomics is a relatively new field, so there’s still much to learn,” said Dzikowski. “We have seen that PRMT5 regulates ATM, a key sensor in DNA repair. Our combination treatment exploits this vulnerability by pairing a PRMT5 inhibitor with an additional DNA repair protein inhibitor, driving cancer cells toward death through accumulated DNA damage.”
For the new study, the researchers began by testing PRMT5 and Chk1 inhibitors on pancreatic cancer cells. They found that the combination treatment slowed cancer cell growth more effectively than either drug alone, suggesting a synergistic effect. They also observed that the combination pushed the cells into apoptosis, or programmed cell death, rather than just pausing growth.
The researchers then tested the drug combination in mice after injecting human pancreatic cancer cells under the skin and allowing tumors to form. The mice receiving the combination therapy showed significantly reduced tumor growth and increased the median overall survival of mice by 40% and 25%, respectively, compared to mice receiving either the PRMT5 or Chk1 inhibitor alone.
The researchers are continuing work aimed at uncovering the many functions of PRMT5 and understanding the mechanisms involved in the effects observed in this study. They note that advancing the combination therapy to human trials for pancreatic cancer would require the completion of rigorous preclinical studies.
“We’re hopeful that PRMT5 inhibitors will continue undergoing development for therapeutic use,” said Dzikowski. “Currently, there are several clinical trials underway to evaluate PRMT5 inhibitors for solid cancers, so we’re optimistic that our work provides a strong foundation for advancing these inhibitors to additional clinical trials in pancreatic cancer.”
Madeline Dzikowski will present this research from 4:30 to 6:30 p.m. CDT on Tuesday, April 15, at the Lakeside Center of the McCormick Place Convention Center. Contact the media team for more information.
About the American Society for Biochemistry and Molecular Biology (ASBMB)
The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Founded in 1906 to advance the science of biochemistry and molecular biology, the society publishes three peer-reviewed journals, advocates for funding of basic research and education, supports science education at all levels, and promotes the diversity of individuals entering the scientific workforce.
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