Crosstalk between the nervous system and tumor microenvironment: Functional aspects and potential therapeutic strategies

Recent advancements in understanding the tumor microenvironment (TME) have highlighted the critical role of the nervous system in cancer progression. This review comprehensively examines how the nervous system influences various aspects of tumorigenesis, including growth, motility, immune response, angiogenesis, and the behavior of cancer-associated fibroblasts (CAFs). We delineate the neurodevelopmental mechanisms associated with cancer, such as the secretion of neurotrophins and exosomes by cancer cells. Furthermore, we explore the emerging therapeutic strategy of targeting nerves associated with tumors. Evidence supporting this approach includes studies demonstrating direct tumor growth inhibition, enhanced efficacy of immunotherapy when combined with nervous system-modulating drugs, and the suppression of tumor blood vessel formation through nerve targeting. Finally, we discuss the current challenges in this field and emphasize the need for further exploration within cancer neuroscience.