Although evidence over the last 30 years suggests that the autonomic nervous system (ANS) mediates
stress-induced allostatic and immune responses, the crucial role that it plays in the tumor micro-environment has
only recently been reported. Here, we review the action of ANS signaling in this micro-environment. Emerging
data suggest that primary tumors are innervated by the ANS which mediates stress-related effects on tumor progression.
The activation of the sympathetic nervous system (SNS) takes advantage of neurotransmitters and neuropeptides
from the innervating neural circuitry and/or hypothalamic-pituitary-adrenal axis glucocorticoids via
their receptors to modulate the gene expression associated with oncogenesis, the proliferation and apoptosis of
tumor cells, angiogenesis, and the tumor-associated immune response. The parasympathetic nervous system has
also been implicated in some tumor types, but its contribution in the tumor micro-environment remains unclear.
In addition to identifying the ANS signaling pathways involved in tumor progression, recent reports suggest that
the ANS could be a potential biomarker to predict tumor progression, and have identified new pharmacological
strategies, such as the use of β-adrenergic blockers, to inhibit tumor progression and metastasis by targeting this
system. These findings are reviewed here.