Cancer Electrified: How Neural Activity Fuels Small-Cell Lung Cancer Progression

In a groundbreaking discovery, researchers have identified intrinsic electrical excitability as a key driver of small-cell lung cancer (SCLC) malignancy. Unlike most cancer cells, which depend on aerobic glycolysis, the neuroendocrine (NE) subpopulation of SCLC cells generates action potentials, leading to an increased reliance on oxidative phosphorylation due to high ATP demands. This metabolic shift is supported by non-NE cells, mirroring the astrocyte-neuron metabolite shuttle in the brain. Additionally, SCLC progression is accompanied by drastic changes in tumor innervation, fostering intratumoral heterogeneity and enhanced neuronal traits, which in turn reinforce cancer progression in a self-sustaining cycle. These findings redefine cancer metabolism and open new avenues for targeting electrical activity in aggressive tumors, offering potential strategies to disrupt the tumor’s metabolic dependencies and halt its spread.