A potential target for experimental drugs that block PRMT5 – a naturally occurring enzyme some tumors rely more on for survival – has been identified by researchers with the Fralin Biomedical Research Institute’s Cancer Research Center in Washington, D.C.<\/p>\n
In a study published this month in\u00a0Cancer Research, Assistant Professor\u00a0Kathleen Mulvaney\u00a0of Virginia Tech’s Fralin Biomedical Research Institute shared research that could help guide development of new therapies for some treatment-resistant lung, brain, and pancreatic cancers.<\/p>\n
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“Using genetic screening, we found a new drug combination that seemingly works.”<\/p>\n
\n <\/p>\nKathleen Mulvaney, Assistant Professor,\u00a0Fralin Biomedical Research Institute, Virginia Tech<\/p>\n
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New therapies are needed. Lung cancer is a leading cause of cancer-related death globally. The five-year survival rate is less than 15 percent for pancreatic cancer patients<\/a>, and even lower for glioblastoma.\u00a0<\/p>\n
“With one drug alone, tumors can become resistant really quickly,” said Mulvaney, who is a member of the research institute’s Cancer Research Center in Washington, D.C. Treatment often fails. The findings\u00a0suggest the PRMT5 inhibitor could\u00a0be a powerful new approach for\u00a0certain\u00a0hard-to-treat\u00a0cancers. “In all cases, the combination is better at killing than the single agents.”<\/p>\n
Many of these\u00a0solid tumors\u00a0share\u00a0a\u00a0genetic trait: They lack CDKN2A\u00a0and\u00a0MTAP, two genes that suppress tumors and help regulate cell growth. Without them, the cancers become dependent on PRMT5 and potentially vulnerable to drugs that block the enzyme.<\/p>\n
Mulvaney and colleagues analyzed genetic data from thousands of cancer patients available through the cBioPortal.<\/p>\n
They applied CRISPR editing tools to look at biological pathways across a range of samples to determine which genes make cancer cells more vulnerable to PRMT5 inhibitors and which combinations could improve response and long-term outcomes.<\/p>\n
An estimated 5 percent of all cancer patients – about 80,000 to 100,000 per year in the U.S. – can benefit from the therapies identified, according to Mulvaney, who also holds an appointment in biomedical sciences and pathobiology in the Virginia-Maryland College of Veterinary Medicine.<\/p>\n
Using PRMT5 inhibitors with drugs that block a communication system that tells cancer cells when to grow, divide, or shut down – known as the MAP kinase pathway – scientists identified potential treatments for clinical trials.\u00a0<\/p>\n
“We also discovered a number of genes that interact with PRMT5 signaling in cancer that were not previously known,” Mulvaney said.<\/p>\n
In addition to lung, brain, and pancreatic cancers, the treatment shows promise for some types of melanoma<\/a> and mesothelioma.<\/p>\n
In both animal models and cell cultures derived from patient tissue, lab members saw success after testing potential therapies.\u00a0<\/p>\n
“In all cases, the combination is better at killing cancer cells than the single agents,” Mulvaney said. “Only the combinations led to complete regressions.”<\/p>\n
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