Cancer Neuroscience: Dissecting Autonomic and Sensory Neural Regulation of Tumor Progression and Therapeutic Resistance.

A bstract The pathological features of invasion and metastasis in malignant tumors are intricately intertwined with the tumor microenvironment (TME). Recent investigations underscore that, alongside immune cells, blood vessels, and the lymphatic system, the nervous system emerges as a pivotal player within the TME. Tumors possess the remarkable ability to modify and even co-opt the architecture and functions of the nervous system, creating a dynamic interplay. Furthermore, aberrant neuronal activation has the potential to accelerate tumor progression. This review summarizes the emerging field of cancer neuroscience, encompassing both direct neuro–cancer cell communication and indirect interactions mediated through other TME components. It further outlines the commonly used experimental tools, cutting-edge technologies, and potential therapeutic targets identified along neuro–cancer interaction pathways. By elucidating the reciprocal interplay between the nervous system and tumors, this area of research offers new perspectives for understanding tumorigenesis and provides promising molecular targets and strategies for cancer therapy. • Integrates advances in oncological neuroscience linking neural activity to cancer progression. • Elucidates how sympathetic, parasympathetic, and sensory nerves regulate tumor immunity and resistance. • Identifies actionable neural–tumor signaling pathways as emerging therapeutic targets. • Highlights open questions and experimental strategies shaping the next phase of neuro–cancer research.