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Abstract
Glioblastoma multiforme (GBM) is the most aggressive glioma, with poor survival despite anti-angiogenic therapy. Resistance mechanisms, including Akt pathway activation and autophagy, limit treatment efficacy. This study evaluated strategies to enhance the receptor tyrosine kinase inhibitor cediranib, which targets VEGF and PDGF receptors. Two novel combinations were tested: cediranib with quinacrine, an autophagy inhibitor, and cediranib with proteasome inhibitor SC68896. Both combinations improved anti-glioma activity in vitro and in vivo, reducing tumor growth and vascularization, increasing necrosis, and prolonging survival. Findings suggest targeting dimerization and survival pathways alongside angiogenesis may offer promising therapeutic approaches for GBM.