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Presentation date

Summer 8-10-2022

College, Institute, or Department

MD-PhD Scholars Program

Faculty Mentor

Nicole Shonka, MD

Research Mentor

Raghupathy Vengoji, Ph.D.

Abstract

Glioblastoma (GBM), a grade IV astrocytoma, is the most aggressive primary brain tumor and the mean adult survival time is a mere 14.6 months. Current treatment options include gross tumor resection, radiation treatment, and chemotherapy. Temozolomide is the standard drug utilized for chemotherapy, but it has a limited effectiveness, as patients commonly develop resistance after two and a half months. With no significant cures or treatments, it is pertinent to explore alternative avenues for disease mitigation. One possible pathway lies in the expression of Nerve Growth Factor Receptor (NGFR). Normally, NGFR is responsible for the differentiation of neurons, and it allows the central nervous system to respond to stimuli. If NGFR is dysregulated, cells begin to proliferate at extremely high rates. This uncontrolled proliferation has an association with the formation of GBM. Upregulation of NGFR in other cancers, specifically melanoma, has been associated with increased tumor resistance to cytotoxic T cells. When NGFR was inhibited in T cell resistant melanoma cell lines, T cell tumor killing levels were heightened. Our bioinformatic analysis using Gene Expression Profiling Interactive Analysis (GEPIA) revealed that NGFR expression significantly increased in GBM when compared to normal brain. RT-PCR analysis results display increased levels of NGFR transcripts in EPG (high grade mouse glioma cell line) when compared to lower grade gliomas. Moreover, our western blot analysis on human and mouse GBM cell lines showed increased expression of NGFR. Interestingly, NGFR inhibitor, AG-879 decreased the proliferation/viability of U251 GBM cells in a dose dependent manner.

Keywords

GBM, NGFR, Therapy resistance

Nerve Growth Factor Receptor Kinase Inhibitor AG-879 Decreases Cell Viability in Glioblastoma Cell Lines

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