Neuron activity-dependent cancer progression.

Abstract

Neuronal activity instructs a broad range of biological processes, including the regulation of cancers of both the central and peripheral nervous systems. Studies across multiple cancer types have established that neuronal activity regulates tumor progression through diverse mechanisms, including direct synaptic communication, neurotransmitter and neuropeptide signaling, activity-dependent paracrine signaling, and bioelectrical signaling. In turn, tumors actively remodel neural circuits through altered neuronal excitability, axonogenesis, neuronal reprogramming, and nerve injury, establishing bidirectional interactions that reinforce malignant progression. Importantly, neural regulation of cancer is highly context-dependent, with the same neural circuits exerting tumor-promoting or tumor-restraining effects depending on the cancer type, disease stage, neuronal subtype, and surrounding microenvironment. Neuron-tumor interactions engage diverse cellular components of the tumor microenvironment, including immune, stromal, vascular, and glial cells, extending neural regulation beyond direct effects on cancer cells. Communication between peripheral tumors and the central nervous system further reveals organism-wide neural regulation of cancer. Together, these findings establish neuronal activity as a fundamental regulator of tumor biology and highlight neuron-cancer signaling and neuromodulation as promising therapeutic targets across diverse malignancies.