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Pharmacological targeting and characterization of Voltage-Gated Sodium Channels (VGSCs) expressed in the high-grade glioma microenvironment

High-grade glioma (HGG) cells reactivate neurodevelopmental programs regulated by ion channels to drive tumor progression. The activity of voltage-gated sodium channels (VGSCs) is fundamental to development, a target of blood-brain barrier (BBB)-permeable FDA-approved drugs, and aids tumor advancement in several cancers. However, the contribution of VGSC activity to HGG pathology remains unknown.

Citation:
Fletcher EV, Shard C, Boyle Y, Milligan CJ, Cross RSN, Jones AC, Francis A, Dewdney B, Barker M, Rezaeiravesh S, Ng ZY, Yeow Y,  ……. Valvi S, Jenkins MR, ……  Johns TG. Pharmacological targeting and characterization of Voltage-Gated Sodium Channels (VGSCs) expressed in the high-grade glioma microenvironment. BMC Cancer. 2026;26(1).

Keywords:
Diffuse midline glioma (DMG); GS967.; Glioblastoma; High-grade gliomas (HGGs); Invasion; Invasiveness; Leading edge; Persistent sodium current (INaP); Voltage-gated sodium channels (VGSCs)

Abstract:
High-grade glioma (HGG) cells reactivate neurodevelopmental programs regulated by ion channels to drive tumor progression. The activity of voltage-gated sodium channels (VGSCs) is fundamental to development, a target of blood-brain barrier (BBB)-permeable FDA-approved drugs, and aids tumor advancement in several cancers. However, the contribution of VGSC activity to HGG pathology remains unknown.