Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion.
The Notch1-mediated signaling pathway has a central role in the maintenance of neural stem cells and contributes to growth and progression of glioblastomas, the most frequent malignant brain tumors in adults.
Current and future strategies in developing tumor-selective therapy using inhibitors of signaling pathways dysregulated in leukemias (FLT3, NOTCH1) and solid/brain tumors (ErbB1-4, IGF-IR, PTCH1), and the challenges in developing less toxic, but equally effective treatments in pediatric oncology are presented.
In addition, pretreatment of glioma cells with Notch-1 or Delta-like-1 small interfering RNA significantly prolongs survival in a murine orthotopic brain tumor model.