Circadian disruption in cancer: a neuroendocrine-immune pathway from stress to disease?

Psychosocial factors may modulate the course of cancer, but few data have been gathered on the biological mechanisms by which these effects may be mediated. We briefly review evidence of psychosocial effects on cancer progression and discuss one potential pathway that may underlie these effects: the disruption of neuroendocrine and immune circadian rhythms. Circadian system alterations occur in tumor tissue, tumor-bearing animals, and cancer patients with greater disruption seen in more advanced cases. Rhythm alterations include diminished amplitude, phase shifts, period changes, and erratic peaks and troughs in endocrine, metabolic, immunological, and rest- activity cycles. Psychosocial factors can engender dysregulation of circadian function. Cancer-related circadian dysregulation may also be driven by genetic factors, environmental and behavioral influences, and effects of the tumor on host clock regulation. There are several mechanisms by which circadian disruption might hasten tumor growth: via direct effects of altered hormone levels on tumor cells, effects on tumor versus host metabolism, neuroimmune effects resulting in cancer-relevant immunosuppression, or reduced efficacy and tolerability of cancer treatments for which the timing of administration is based upon the assumption of normal circadian rhythms. Emerging data in the human and animal literature suggest that circadian regulation may be an important prerequisite for the maintenance of host defenses against cancer. Thus, stress-related circadian disruption may have negative implications for cancer prognosis. Psychosocial effects on cancer progression may be measured, and possibly mediated, by disruption of circadian function.