Entangled cellular and molecular relationships at the sensory neuron-cancer interface.

Abstract

Peripheral sensory neurons, once regarded merely as a passive route for nociceptive signals, are now acknowledged as active participants in solid tumor progression. This review explores how sensory neurons influence and are influenced by the tumor microenvironment (TME) through both chemical and electrical signaling, underscoring their pivotal role in the emerging field of cancer neuroscience. We summarize recent findings indicating that cancer-neuron interactions vary among different organs and experimental models, highlighting the ways in which various tumors recruit and reprogram sensory neurons to establish mutual communication loops that foster malignancy. Clinically, the degree of sensory innervation and the level of neuropeptide signaling show promise as diagnostic and prognostic biomarkers, while targeting these pathways may enhance the efficacy of standard cancer treatments. This review also highlights current knowledge gaps and proposes future research directions aimed at disrupting sensory neuron-tumor interactions, with the ultimate goal of improving clinical outcomes across multiple cancer types.