A potential target for experimental drugs that block PRMT5 \u2014 a naturally occurring enzyme some tumors rely more on for survival \u2014 has been identified by researchers with the Fralin Biomedical Research Institute\u2019s Cancer Research Center in Washington, D.C.<\/p>\n
In a study published this month in\u00a0Cancer Research<\/a>, Assistant Professor Kathleen Mulvaney<\/a> of Virginia Tech\u2019s 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 \u201cUsing genetic screening, we found a new drug combination that seemingly works,\u201d Mulvaney said.<\/p>\n 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 and even lower for glioblastoma.\u00a0<\/p>\n \u201cWith one drug alone, tumors can become resistant really quickly,\u201d Mulvaney said. Treatment often fails. The findings\u00a0suggest the PRMT5 inhibitor could\u00a0be a powerful new approach for\u00a0certain\u00a0hard-to-treat\u00a0cancers. \u201cIn all cases, the combination is better at killing than the single agents.\u201d<\/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 \u2014 about 80,000 to 100,000 per year in the U.S. \u2014 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 \u2014 known as the MAP kinase pathway \u2014 scientists identified potential treatments for clinical trials.\u00a0<\/p>\n \u201cWe also discovered a number of genes that interact with PRMT5 signaling in cancer that were not previously known,\u201d said Mulvaney, who is a member of the research institute’s Cancer Research Center in Washington, D.C.<\/p>\n In addition to lung, brain, and pancreatic cancers, the treatment shows promise for some types of melanoma 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 \u201cIn all cases, the combination is better at killing cancer cells than the single agents,\u201d Mulvaney said. \u201cOnly the combinations led to complete regressions.\u201d<\/p>\n The research was supported by a postdoctoral training fellowship and investigators\u2019 research award from the National Institutes of Health as well as grant funding from the its National Cancer Institute. The study also received support and funding awards from the Broad Institute; the V Foundation; the Claudia Adams Barr Program and Hale Family Center for Pancreatic Cancer Research, both of the Dana-Farber Cancer Institute; and DAAD Promos and Marshall Plan scholarships.<\/p>\n