What is the Relevance of Neuron-Tumor Interactions in Malignant CNS Tumors?

Benarroch, Eduardo · Neurology · 2026

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Abstract

Crosstalk between neurons and tumor cells strongly affects tumor growth, invasion, metastasis, and resistance to treatment. In the CNS, connections between neurons and malignant tumor cells promote cell proliferation. Glutamatergic or GABAergic neurons promote glioblastoma growth through neuron-to-glioma synapses and through activity-dependentparacrine signals. Glioblastoma cells form an interconnected network for signal propagation and synaptically integrate into neural circuits. Brain metastasis, for example, from breast cancer, acquire neuronal-like features within the neural microenvironment and also exploit neural circuitry by forming ''pseudotripartite synapses'' where cancer cells receive glutamatergic input facilitating their growth and colonization within the brain. These interactions between neurons and malignant cells in the CNS provide potential therapeutic targets.

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