Abstract
OBJECTIVE: The role of the sympathetic nervous system (SNS) in tumor development, progression and metastasis is studied for more than half a century and is attracting more attention during the last years. In this narrative review, we aim to a chronological and methodological presentation of the most interesting and pioneering studies on the subject. METHODS: The complexity of the autonomic nervous system's interaction with the immune system, its direct and indirect effects on tumors and their surrounding tissues, plus the diversity and heterogeneity in the design and methodology of the studies, provide hard-to-interpret data and, at times, controversial findings. Studies are categorized into four main groups regarding the distribution of sympathetic nerve fibers inside the tumor, the effect of sympathectomy on cancer progression, the role of neurotransmitters on tumor growth and the impact of sympathetic adrenergic signaling on the anti-tumor immune response. RESULTS: Studies from all four categories converge to a common point. There is strong evidence that SNS function plays a role in the development and progression of tumors and subsequently the modification of SNS function, locally or diffusely, can affect the course of tumor growth. CONCLUSION: The impact of SNS function on cancer behavior may be exerted in two ways, directly via the sympathetic nerve fibers or through widely distributed neurotransmitters. Modification of them, combined or not with treatments altering the immune function, could be the target for future therapeutic implications.