Gene regulation of DNA repair and drug resistance in aggressive brain tumors

S cells exhibit higher levels of MGMT compared to M cells, which is associated with reduced sensitivity to temozolomide.

• MGMT promoter methylation is a predictive biomarker for response to alkylating chemotherapy in glioblastoma.
• Glioma-initiating cells (GIC) with stem-like features show increased MGMT expression compared to differentiated cells.
• Transitioning GIC from sphere to adherent cultures leads to decreased MGMT expression and heightened sensitivity to temozolomide.
• Increased expression of the NF-κB pathway components p50/p65 is observed in S cells, correlating with MGMT overexpression.
• Inhibition of NF-κB reduces MGMT levels, suggesting a role in alkylator resistance in this glioma stem-like cell model.

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