Brain-cancer interactions outside the CNS.

Emerging research highlights the key role of the central nervous system in regulating peripheral tumor progression via neural, neuroendocrine, and immune pathways. Although direct evidence linking the brain to peripheral tumor initiation remains limited, recent studies using retrograde tracing have revealed anatomical and functional circuits between specific brain regions and peripheral solid tumors. These circuits influence malignant, stromal, and immune cells within the tumor microenvironment, as well as systemic immune and metabolic processes. In this review, we synthesize current findings on brain-periphery neural networks across multiple cancer types and discuss how tumor burden can reshape brain activity, contributing to emotional and cognitive disturbances, and how the brain, in turn, regulates tumor biology. In particular, we address the translational potential of targeting brain-tumor circuits via neuromodulation, behavioral interventions, and lifestyle-based therapies. Understanding these bidirectional communications offers new approaches for systemic, integrative therapeutic strategies.