Tracking Tumor Regression in ENO1-Deleted Glioblastoma via IVIS Spectrum



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Glioblastoma (GBM) is a fast-growing and aggressive form of brain cancer arising from astrocytes, which are the star-shaped cells that form the supportive tissue of the brain. In GBM, the glycolytic gene Enolase 1 (ENO1) in the 1p36 locus is deleted, but this loss is tolerated through the expression of Enolase 2 (ENO2). Previous work in research has shown that the selective inhibition of ENO2 (both genetically and pharmacologically) can lead to GBM tumor stasis, regression, and/or eradication. Altering the structural activity of the potent natural Enolase inhibitor SF2312 forms the active drug HEX, which becomes the prodrug POMHEX through the addition of Pivaloyloxymethyl (POM) groups that neutralize the negative charge of the phosphonates and make the drug more lipid-soluble, allowing it to cross cell membranes and become even more effective in terms of potency. To test the efficacy of various drugs (POMHEX, DMSO, HEX, and PBS) on mice with D423 GBM tumors, the IVIS Spectrum was used to analyze the bioluminescent signals from tumors. Based on the data, POMHEX selectively kills ENO1-deleted GBM cells through the inhibition of glycolysis, making it an effective anti-tumor therapeutic strategy. This project was completed with contributions from Sunada Khadka, Naima Hammoudi, Yu-His Lin, and Florian Muller from the MD Anderson Cancer Center.