Hijacking of neural circuits by malignant glioma: mechanistic insights and clinical implications

Glioblastoma and other malignant gliomas are characterized by high heterogeneity that drives their aggressiveness and contributes to poor clinical outcomes. Understanding the mechanisms behind glioma malignancy, as well as the crosstalk between these tumors and their microenvironment, may hold transformative clinical relevance. Recent findings show that glioblastoma cells interact in bidirectional and multimodal crosstalk with the neuronal compartment of the microenvironment. While the knowledge on these complex interactions is still limited, it is now clear that dynamic communications include responses to neuronal activity-dependent molecules, synaptic signaling, and remodeling of neural circuits. Together, these direct and indirect dialogues promote glioma cells proliferation and invasion, effectively hijacking neuronal activity to fuel tumor aggressiveness. This review focuses on the bidirectional interaction between neurons and malignant glioma cells, highlighting its clinical relevance and potential to guide the development of novel precision therapies specifically targeting the glioma-neuron crosstalk.