Ohio State researchers could lead the way to improved treatment for a deadly form of brain cancer. An international multi-center study led by The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) has identified an enzyme called phosphoglucomutase3 (PGM3) as a favorable target for treating glioblastoma, the most lethal primary brain tumor. Deliang Guo, PhD, director of the Center for Cancer Metabolism and member of the Translational Therapeutics Program at the OSUCCC – James, was corresponding author for the study, which was published in the journal Science Advances. Click here to learn more about brain cancer, including risks, symptoms and treatment options at The Ohio State University. In their journal article, the scientists state that GBM has a median survival of only 12-16 months from diagnosis despite extensive treatments. They note that therapy for this cancer “has shown no substantial changes over the past 20 years,” due mainly to “our incomplete understanding of GBM’s complex biology, which impedes the discovery of effective molecular targets.” The researchers explain that, when elevated, a biological pathway called hexosamine biosynthesis fuels tumor growth by aiding glycosylation, a process in which sugar molecules are added to proteins and lipids (fats). “But which enzyme in this pathway is better to serve as an antitumor target remains unclear,” they write. When examining several of the enzymes within human GBM cell lines and GBM mouse models, they found that inhibiting PGM3, which controls the flux of hexosamine biosynthesis, can diminish the expression of other enzymes in this pathway while also suppressing a critical transcription factor known as SREBP-1, thus thwarting GBM growth. (A transcription factor is a protein that regulates the transfer of genetic information from DNA to RNA in cells.) Click here to learn more about cancer research at the OSUCCC – James. “In this study, we identified PGM3 as a promising target for treating this deadly cancer,” the scientists conclude. “We also uncovered a previously unknown SREBP-1 activation-hexosamine biosynthesis feedback loop that propels rapid GBM growth, and we demonstrated that targeting PGM3 disrupts this loop.” They believe that this approach holds promise not only to better treat GBM but possibly other cancers that also have high demand for being fueled by hexosamine and lipid production. “This study provides a compelling rationale for developing small molecular inhibitor drugs to target the PGM3 enzyme activity as a potential treatment for GBM and other malignancies,” Dr. Guo says. “Moving forward, our team plans to screen and design specific inhibitors to achieve this therapeutic goal.” Click here to learn more about cancer clinical trials at The Ohio State University.