Neural activity is now known to play a major role in cancer growth. Neurons establish synapses with glioma cells and engage with them via paracrine signaling as well to fuel brain tumor growth. Outside the brain, the innervation of a wide variety of tumors—such as those of the breast and prostate—can also regulate their progression. Researchers co-led by Ludwig Stanford’s Michelle Monje reported in a September Nature paper that neuronal activity plays a critical role in the pathogenesis of small-cell lung cancer (SCLC). Michelle and her colleagues showed that severing the vagus nerve—which runs between the brain and lung—in a mouse model of inducible SCLC markedly inhibited the initiation and progression of the tumors, highlighting a critical role for innervation in the earlier phases of their growth. In the brain, a favored locale for SCLC metastasis, they found that SCLC cells co-opt neuronal activity-regulated mechanisms to stimulate their growth and progression. Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drive proliferation of SCLC in the brain through both paracrine and synaptic interactions. The synapses established with a subset of SCLC cells transmit neural signals and the depolarization of their membranes in that process suffices to drive the growth of the brain metastases. Tumor growth, they reported, could be attenuated with an antiseizure drug in the mice.
Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis
Nature, 2025 September 10