Glioma-neuron interactions: from basics to therapy

High-grade gliomas are the most aggressive brain tumors because of their invasive nature and resilience. Recent advances have shown that glioma cells form synapse-like contacts with neurons, responding to neuronal activity and promoting tumor growth. Glioma-neuron communication is initiated by the release of neurotrophic factors from tumors that exploit host neuronal plasticity mechanisms, subsequently inducing the formation and electrical activity of neuron-glioma synapses. Here, we review the evidence supporting functional neuron-glioma interactions and the molecular regulators underlying neuronal plasticity. Furthermore, we discuss the effects of cancer on neural circuits and the possible prognostic value of connectome studies. Finally, we outline therapeutic strategies and challenges in targeting the neuron-glioma interface to reduce brain cancer progression.