Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities

A growing body of research suggests a bidirectional interaction between cancer and the nervous system. Neural cells exert their effects on tumors by secreting neurotransmitters and cell adhesion molecules, which interact with specific receptors on tumor cells to modulate their behavior. Conversely, tumor-secreted factors, particularly including inflammatory factors, can alter neural activity and increase neuronal excitability, potentially contributing to neurological manifestations such as epilepsy. The immune system also serves as a crucial intermediary in the indirect communication between cancer and the nervous system. These insights have opened promising avenues for novel therapeutic strategies targeting both tumors and their associated neurological complications. In this review, we have synthesized the key biological mechanisms underlying cancer-nervous system interactions that have emerged over the past decade. We outline the molecular and cellular pathways mediating this cross-talk and explore the clinical implications of targeting the nervous system to suppress tumor growth and metastasis, mitigate neurological complications arising from cancer progression, and modulate the immune response through neural regulation in the context of cancer therapy.