Mechanisms and therapeutic implications of glioma-neuron interactions

Glioma is the most common type of primary brain tumor and is almost always fatal. The challenge to develop more effective treatments lies in its high invasiveness and solid intratumoral heterogeneity, as well as its insensitivity to traditional radiotherapy and chemotherapy. With the rise of cancer neuroscience, mounting evidence has uncovered a multi-layered and dynamically complex network of communication between glioma cells and neurons which has given us new insights into tumor progression. The nervous system is now recognized as not merely a passive victim of tumor invasion, but as an active modulator and perhaps even driver of glioma progression. In this review, we systematically summarize the interaction of glioma with neuron mechanisms, including synaptic, electrophysiological, paracrine, metabolic, and neurotransmitter-related pathways. In addition, we investigate the extent to which these interactions are associated with gliomas and reveal their potential as therapeutic targets, thereby offering a theoretical foundation and new strategies for the precision treatment of glioma. Taken together, the cross-talk between gliomas and neurons is a dynamic, multi-level, multi-pathway co-regulated network system. Further exploration of this network may promote transformation from a tumor-focused to a tumor-neuron network-based therapeutic plan and provide new prospects for precision medicine.