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New Combination Therapy Shows Potential Against Treatment-Resistant Cancers
Last reviewed: 27.07.2025
A potential target for experimental drugs that block PRMT5, a natural enzyme that some tumors particularly rely on for survival, has been identified by scientists at the Fralin Biomedical Institute Cancer Research Center in Washington.
In a study published in the journal Cancer Research, Associate Professor Kathleen Mulvaney of Virginia Tech's Fralin Biomedical Institute presented data that could help develop new therapies for treatment-resistant forms of lung, brain and pancreatic cancer.
"Using genetic screening, we found a new drug combination that appears to work," Mulvaney said.
The need for new approaches
Lung cancer is one of the leading causes of cancer death worldwide. The five-year survival rate for pancreatic cancer is less than 15%, and for glioblastoma it is even lower.
“When you use just one drug, tumors become resistant very quickly,” said Mulvaney, a member of the Washington Cancer Center. “Often, the treatment doesn’t work. Our results show that a PRMT5 inhibitor could be a powerful approach for hard-to-treat tumors. In any case, the combination works better than the single drugs.”
Genetic vulnerability of tumors
Many of these solid tumors share a common genetic feature: they lack the CDKN2A and MTAP genes, which suppress tumor growth and regulate cell division. In their absence, cancer cells become dependent on the PRMT5 enzyme and, therefore, more vulnerable to drugs that block this enzyme.
CRISPR Applications and Genetic Analysis
Mulvaney and her colleagues analyzed genetic data from thousands of cancer patients available through the cBioPortal platform.
Using CRISPR technology, the researchers studied biological pathways in different samples to determine:
- which genes make cancer cells more vulnerable to PRMT5 inhibitors;
- what drug combinations can enhance the treatment effect and improve long-term results.
Mulvaney estimates that up to 5 percent of all cancer patients in the U.S. (roughly 80,000 to 100,000 people per year) could benefit from this approach. Mulvaney also holds a chair in biomedical sciences and pathobiology at the College of Veterinary Medicine of Virginia and Maryland.
New therapeutic targets
In their work, the scientists used PRMT5 inhibitors in combination with drugs that block the MAP kinase signaling pathway, a signaling system that controls cell growth, division, and death, to identify potential pathways for clinical trials.
"We also found a number of genes that interact with PRMT5 in a tumor context that were not previously known," Mulvaney said.
Potential for other cancers
In addition to lung, brain and pancreatic cancer, the method has also shown promise in some forms of melanoma and mesothelioma.
In experiments both in animal models and in cell cultures obtained from patient tissues, combinations of drugs have demonstrated successful results.
"In all cases, the combination of drugs was better at killing cancer cells than the individual drugs," Mulvaney said. "Only the combination resulted in complete tumor regressions."