Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk

Reciprocal crosstalk between the nervous system and malignancies is increasingly recognized as a key regulator of tumor progression across solid cancers. Neuronal activity and nerve infiltration can shape tumor growth, immune tone, and metastatic behavior through paracrine signaling and, in selected contexts, synapse-like interactions. However, how neural circuits regulate lung cancer progression remains insufficiently defined. β-adrenergic blockade has been reported to be associated with reduced lung tumor growth and metastatic potential in multiple settings, highlighting the clinical relevance of innervation. Here we synthesize emerging evidence on lung cancer-nerve crosstalk from the perspective of cancer neuroscience, focusing on neural remodeling in the tumor microenvironment, mechanisms underlying tumorigenesis and metastasis, the neuro-immune-tumor axis, and translational opportunities for neuro-modulatory interventions. This review provides an integrated framework to inform future mechanistic studies and the development of therapeutically actionable targets.