Drug repurposing of Clofoctol in xenograft glioma model
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Yonk, Marybeth
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Holder, Mary
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Abstract
Glioma, a malignant central nervous system cancer, has a 35% 5-year survival rate. Creating novel therapeutics to treat glioma is hindered by the presence of tumor heterogeneity between patients and clinical trial challenges. The method of drug repurposing of FDA-approved drugs accelerates glioma treatment development by allowing bypass of phase I clinical trials. Based on preliminary work and a specialized method known as high-throughput screening, Clofoctol, a previously FDA-approved respiratory drug, has shown potential as a treatment for glioma by specifically targeting the p53 pathway. A xenograft model using spinal cord glioma cells in immunocompromised nude mice was used to analyze the effectiveness of different concentrations of Clofoctol on glioma tumors over a 10-day treatment period. Clofoctol suppressed tumor growth of glioma cells in the xenograft model shown through immunohistochemistry (IHC) and Hematoxylin and eosin (H&E) staining. RNA sequencing identified normalized cancer-related gene pathways in Clofoctol-treated groups. Together, the data support that Clofoctol worked as a repurposed drug to significantly inhibit tumor growth by suppressing cell proliferation in vivo and should be analyzed further as a clinical therapeutic to treat glioma.
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Undergraduate Research Option Thesis