abstract: does LDN halt tumor growth by regulating circadian cycles?

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Brain Behav Immun. 2003 Oct;17(5):321-8. Related Articles, Links

Circadian disruption in cancer: a neuroendocrine-immune pathway from

stress to disease?

Sephton S, Spiegel D.

Graham Brown Cancer Center, Department of Psychiatry and

Behavioral Sciences, University of Louisville School of Medicine, 500

South Preston Street, room 210, Louisville, KY 40202, USA.

Sephton@...

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.