LAUSR

Abstract Recent data have demonstrated extensive autonomic nervous system (ANS) neural participation in malignant tumors and infiltration of nerve fibers in and around malignant tumors. ANS cybernetic imbalances deriving from central nervous system (CNS) stress are associated with poorer patient outcome and may play a key role in tumor expansion. The ANS modulates and can destabilize tissue stem cells, and it drives the expression of neurotransmitter receptors on tumor cells. Disruption of tumor innervation and pharmacological ANS blockade have abrogated cancer growth in preclinical models. The present review interprets recent key findings with respect to the ANS and cancer. We highlight new data from animal models addressing specific cancers suggesting that unbalanced autonomic cybernetic control loops are associated with tissue instability which in turn promotes, (1) cancer stem cell based tumor initiation and growth, and (2) metastasis. We posit that identifying the sources of neural control loop dysregulation in specific tumors may reveal potential targets for antitumor therapy. Given the striking tumor regression results obtained with gastric vagotomy in gastric cancer models, and the effects of β-adrenergic blockade in pancreatic tumor models, it may be feasible to improve cancer outcomes with therapeutics targeted to the nervous system.