The excitatory milieu in glioma: Mechanisms and therapeutic avenues

Abstract Gliomas are the most common primary malignant brain tumors. Their electrobiologic properties drive disease development, and in select tumors, aberrant neurosignaling is situated at the crux of gliomagenesis and glioma-related epilepsy. Tumor microtubes and the neuronal-glioma synapse are defined components of the glioma circuitry. The nidus of cortical hyperexcitability—the peri-glioma—undergoes severe alterations during disease progression and is influenced by genetic mutations, anomalous synaptic remodeling, inflammatory changes, and an imbalance in neurotransmitters. Such pathologic mechanisms have been exploited for anticancer and anti-seizure value wherein a subset remains to be explored. In this Review, we discuss the hyperexcitable conditions within the glioma microenvironment and candidate therapies for seizure and tumor control.