Ion Channels in Gliomas-From Molecular Basis to Treatment

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2530
• Main Authors: Elias, Abdallah F, Lin, Bernice C, Piggott, Beverly J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-01-2023; MDPI
• Subjects: Angiogenesis; Apoptosis; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain tumors; Chromosomes; Gene expression; glioblastoma; Glioma; Glioma - drug therapy; Glioma - genetics; Humans; Ion channels; Ion Channels - metabolism; ion exchanger; ion transporter; Metastases; Mutation; Nervous system; Neuronal-glial interactions; Neurons; Neurons - metabolism; Neurophysiology; Review; Seizures; Therapeutic targets; Tumor Microenvironment; Tumors; ion transporter; blood–brain barrier; glioblastoma; angiogenesis; ion exchanger; glioma; brain cancer; tumor microenvironment; tumor-associated epilepsy; drug target; ion channels; treatment resistance
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032530

Ion channels provide the basis for the nervous system's intrinsic electrical activity. Neuronal excitability is a characteristic property of neurons and is critical for all functions of the nervous system. Glia cells fulfill essential supportive roles, but unlike neurons, they also retain the ability to divide. This can lead to uncontrolled growth and the formation of gliomas. Ion channels are involved in the unique biology of gliomas pertaining to peritumoral pathology and seizures, diffuse invasion, and treatment resistance. The emerging picture shows ion channels in the brain at the crossroads of neurophysiology and fundamental pathophysiological processes of specific cancer behaviors as reflected by uncontrolled proliferation, infiltration, resistance to apoptosis, metabolism, and angiogenesis. Ion channels are highly druggable, making them an enticing therapeutic target. Targeting ion channels in difficult-to-treat brain tumors such as gliomas requires an understanding of their extremely heterogenous tumor microenvironment and highly diverse molecular profiles, both representing major causes of recurrence and treatment resistance. In this review, we survey the current knowledge on ion channels with oncogenic behavior within the heterogeneous group of gliomas, review ion channel gene expression as genomic biomarkers for glioma prognosis and provide an update on therapeutic perspectives for repurposed and novel ion channel inhibitors and electrotherapy.