Glioblastoma stem cell (GSC) (GSC)

Glioblastoma stem cells (GSCs) are a specialized subpopulation of cells within glioblastoma and other high-grade CNS tumors that possess stem-like properties, including the capacity for self-renewal and the ability to differentiate into multiple neural lineages. These cells are considered the primary drivers of tumor initiation, progression, and the inevitable recurrence observed after standard-of-care treatments like surgery and chemoradiation. GSCs are notably resistant to conventional therapies due to enhanced DNA repair mechanisms, high expression of drug efflux transporters, and their residence in protective niches such as the perivascular and hypoxic zones. Therapeutic strategies targeting GSCs focus on disrupting critical developmental signaling pathways—such as Notch, Wnt, and Hedgehog—or utilizing immunotherapy to target GSC-specific surface markers like CD133. However, the high degree of plasticity and heterogeneity within these cell populations remains a significant challenge for achieving durable clinical responses.

Other names

Brain tumor stem cellsBTSCsGlioma stem-like cellsCNS tumor-initiating cellsGlioblastoma-initiating cellsCNS embryonal stem cells

Therapeutic strategies targeting these cells involve the inhibition of developmental signaling pathways (Notch, Wnt, Hedgehog) to block self-renewal, the use of small molecules to disrupt survival signaling (PI3K/AKT/mTOR), and the application of immunotherapies (CAR-T, monoclonal antibodies) directed against specific surface markers to induce cell death or differentiation.