In vitro and in vivo characterization of the combinatorial effect of Axitinib and N-acetyl cysteine treatment in glioblastoma.

Glioblastoma IDH-wildtype (GBM) is the most aggressive brain tumor, with a peculiar ability to induce neoangiogenesis and cause relapses after surgical resection, due to the presence of tumor stem cells, which are resistant to chemotherapy. Axitinib (Axi) is an orally available kinase inhibitor, with high specificity for vascular endothelial growth factor receptors 1,2, and 3 (VEGFR-1, -2, -3) and it is already in use for several types of cancer. It has been previously shown that following Axi treatment, both GBM and normal cells undergo senescence. It has also been demonstrated that co-treatment with the antioxidant N-acetylcysteine (NAC) inhibits the induction of the senescent phenotype selectively in normal cellular contexts, without altering the induction of senescence in tumorous ones [1]. The aim of the present study is to verify if the co-administration of NAC with Axi leads to a reduction of the Axi-dependent damage of normal cells, without influencing the efficacy of the drug on tumor cells, in both glioblastoma stem cells (GSCs) and GBM in vivo model.