Abstract 1515: Inhibition of the IKK/NF-κB pathway impairs glioma stem cell function

Abstract Glioma, the most frequently occurring primary brain tumor, has a median survival of less than 15 months, despite multimodal treatment combining surgery, radiation, and chemotherapy. It has been suggested that the presence of cancer stem cells (CSCs) within these tumors are responsible for resistance to treatment and high probability of recurrence. As a result, there is increasing interest in specifically targeting CSCs with new therapies to improve treatment of this disease. NF-κB has been implicated in numerous forms of cancer, as its target genes regulate hallmarks of cancer such as cell proliferation, survival, and invasion. Both glioma cell lines and tumor samples show high levels of phosphorylated p65, a marker of NF-κB activation. When comparing populations from tumor explants, NF-κB is preferentially activated in the CSC subset. We are examining the effects of IKK/NF-κB inhibition on both heterogeneous glioma explants and purified (CD133+) CSCs from these explants. Inhibition of NF-κB through either genetic or pharmacological means abrogates neurosphere formation, an in vitro measure of stem cell function. Additionally, real-time PCR analysis indicates that inhibition of NF-κB leads to a decrease in target genes implicated in glioma CSC biology, such as A20 and IL-6. Through gene expression analysis, we have identified a set of NF-κB-dependent genes that potentially contribute to the CSC phenotype, including invasion. We are using ex vivo brain slices and in vivo xenograft models to examine our findings in a pre-clinical setting. Our studies indicate a significant role for the NF-κB pathway in the biology of glioma CSCs, with possible parallels in CSCs of other tumor types. Citation Format: Amanda L. Rinkenbaugh, Patricia C. Cogswell, Albert S. Baldwin. Inhibition of the IKK/NF-κB pathway impairs glioma stem cell function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1515. doi:10.1158/1538-7445.AM2015-1515