Notch signaling (NS) is one of the primary regulators of Glioblastoma (GBM), which shapes tumour growth and evolution while protecting against drug treatments. Notch signaling enables Glioma stem cell (GSC) preservation in tumours, enhancing their diversity, and increasing tumour strength and resistance to treatment. Notch signaling keeps cancer cells growing and active through its ability to halt cell development while maintaining links with critical tumour pathways Wnt/β-catenin, PI3K/AKT, NF-kB, Hedgehog, and TGF-β. When signaling molecules communicate, they develop a strong system that enables tumour cells to survive longer and establish new blood vessels while resisting immune defenses and treatments. Developing treatments consisting of γ-secretase inhibitors, antibodies, and small molecule inhibitors show better outcomes when combined with other pathway-targeting approaches. Notch signaling may promote or inhibit cancer cell proliferation; it is crucial to detect unique biomarkers for each patient before developing individualized therapy regimens. The treatment of Notch-dependent tumours with PI3K/AKT or TGF-β inhibitors helps reduce resistance to therapy. The development of molecular techniques and single-cell analysis enables us to understand Notch signaling better for inventing treatment options specific to clinical settings. These approaches could be combined to improve the quality of life and speed up the recovery process for GBM patients. Notch signaling presents difficulties and possibilities that can guide new treatment options for GBM.
Keywords: Glioblastoma; Notch Signaling; Signaling interaction; Tumor Heterogenicity; and Glioma Stem cells.
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