Cancer neuroscience explores how the nervous system influences tumor development. In primary brain tumors like glioma and glioblastoma, neurons promote growth through factors such as BDNF and neuroligin-3. Glioma cells form excitatory synapses with neurons and develop neuronal-like features, including “tumor microtubes” that facilitate communication and proliferation.
Outside the brain, the peripheral nervous system regulates the tumor microenvironment. Tumors exploit neural signaling for growth and spread, inducing axonogenesis and migrating along nerves in peri-neuronal invasion, which worsens prognosis. The sympathetic nervous system accelerates progression via β-adrenergic signaling, affecting DNA repair, inflammation, and metastasis.
Brain metastases, often from lung, breast, or melanoma, face challenges from the blood-brain barrier and rely on neuron-like properties for survival. Metastatic cells interact with neurons via glutamatergic synapses (NMDA and AMPA receptors), and disrupting these interactions reduces tumor growth. Astrocytes and the brain’s metabolite environment further modulate metastatic survival and proliferation.
Understanding these neuron-tumor interactions highlights synaptic contacts and neurotransmitter signaling, especially glutamate, as promising therapeutic targets.