The role of the vagus nerve in cancer prognosis

The role of the vagus nerve in cancer prognosis and effects of non-invasive vagal stimulation on inflammatory and tumor markers.

 

The understanding of oncogenesis has evolved from an emphasis on transformed cells and mutations alone, to the complex interplay between mutations and tumor microenvironments. Inflammatory signals, oxidative stress and sympathetic neurotransmitters in the tumor microenvironment play crucial roles in early and in later stages of tumor development. The vagus nerve can modulate and inhibit all three of these mechanisms – inflammation, oxidative stress and sympathetic neurotransmitters. Thus, we hypothesize that vagal nerve activity may inhibit tumor growth.
Furthermore, low vagal activity (indexed by heart rate variability (HRV)) predicts poorer prognosis in cancer, which is in line with the hypothesized neuro-modulatory role of the vagus nerve in cancer. However, the effects of non-invasive vagal activation on tumor growth and on tumor markers have not been evaluated in humans.

This research aims to extend the investigation of the role of vagal activity in cancer prognosis and to test the hypothesized underlying mechanisms in clinical trials. First it will be tested whether HRV predicts prognosis in several cancers, independent of confounders. More precisely, the hypothesis is that high HRV correlates with better survival of certain cancers. This work currently ongoing. Second, the effects of 2 non-invasive vagal-activating interventions, namely transcutaneous vagus nerve stimulation and heart-rate variability biofeedback, on HRV were tested in healthy people. In this population group, decreased vagal activity, higher values of inflammation and norepinephrine, and oxidative stress, have been found previously. Furthermore, the effects of an acetylcholinesterase-inhibitor drug on survival in rats with a tumor will be investigated. The final and ultimate study will measure the effects of the vagal activating intervention on biomarkers and on a tumor marker in cancer patients. This research will investigate the potential role of the vagus nerve stimulation in cancer treatment.