The combination significantly reduces the frequency of glioblastoma stem cells (GSCs) compared to either drug alone, especially in ATO-resistant models.<h4>Results</h4>These observations suggest that targeting the MNK1 pathway in conjunction with ATO is a promising strategy to specifically eradicate GSCs, which are major drivers of GBM recurrence and therapeutic failure. This evidence concerns the gene MKNK1 and glioblastoma.