High-grade glioma (HGG) is an aggressive brain cancer with an overall ۵-year survival rate of less than ۱۰% in adults and less than ۲% in children. Despite significant research efforts, surgery combined with chemo- and radiotherapy is the only treatment option available for these patients. New targeted therapies such as kinase inhibitors, and combined modalities fail in clinical trials due to the inability of drugs to cross the blood-brain barrier, and HGG pathway rewiring. In vitro studies suggest that ion channels contribute to HGG pathway rewiring and tumor survival. There are several United States Food and Drug Administration-approved neurological drugs that readily cross the blood-brain barrier and target ion channels. These drugs are readily available on the shelf and can be easily repurposed to treat HGG. A systematic understanding of the oncogenic roles of ion channels in patients with HGG will help us to repurpose ion channel drugs to treat HGG. The study of the oncogenic potential and therapeutic targeting of ion channels in HGG is still in the early stage. This review summarises the findings that elucidate the expression and oncogenic potential of ion channels in HGG patients. We have identified the research gaps to translate ion channels as therapeutic targets for HGG. Finally, we highlight the potential to use ion channel drugs as a single agent or as part of combination therapy for the treatment of patients with HGG.High-grade glioma (HGG) is an aggressive brain cancer with an overall ۵-year survival rate of less than ۱۰% in adults and less than ۲% in children. Despite significant research efforts, surgery combined with chemo- and radiotherapy is the only treatment option available for these patients. New targeted therapies such as kinase inhibitors, and combined modalities fail in clinical trials due to the inability of drugs to cross the blood-brain barrier, and HGG pathway rewiring. In vitro studies suggest that ion channels contribute to HGG pathway rewiring and tumor survival. There are several United States Food and Drug Administration-approved neurological drugs that readily cross the blood-brain barrier and target ion channels. These drugs are readily available on the shelf and can be easily repurposed to treat HGG. A systematic understanding of the oncogenic roles of ion channels in patients with HGG will help us to repurpose ion channel drugs to treat HGG. The study of the oncogenic potential and therapeutic targeting of ion channels in HGG is still in the early stage. This review summarises the findings that elucidate the expression and oncogenic potential of ion channels in HGG patients. We have identified the research gaps to translate ion channels as therapeutic targets for HGG. Finally, we highlight the potential to use ion channel drugs as a single agent or as part of combination therapy for the treatment of patients with HGG.
