Melatonin Cancer Therapy

Abstract

Melatonin prevents and delays chemical carcinogenisis and cancer growth in vivo in the mouse and rat. Blind people have robust, albeit mostly free-running melatonin circadian rhythms and they are at lower risk for the development of many, if not all, cancers. Women with breast cancer and men with prostate cancer have diminished nighttime melatonin secretion.

Each proven melatonin biological effect — the transduction of circadian and circannual temporal information from the environmental light/dark schedule to each cell within the body, the induction and enhancement of sleep, the diminishment of core body temperature, and the resetting of circadian clocks — is entirely dependent upon the temporal context, i.e., the circadian/circannual stage of melatonin availability/administration. The host-cancer balance is likewise rhythmically coordinated in time by endogenous and exogenous circadian and circannual internal pacemakers and external zeitgebers. Each of the targets of cancer treatment is differentially available in both normal host cells and cancer cells at different times within these biological cycles. This chronobiology is faithfully reflected by the fact that the circadian/circannual timing of cancer chemotherapy determines to a medically meaningful extent the damage done to normal cells, the amount of drug that can be safely given, and the antitumor efficacy of that drug.

Giving a chronobiotic agent, like melatonin, without regard to its circadian/ circannual scheduling is not logical and should not be expected to reveal its true utility as an anticancer agent. Despite the fact that the timing of melatonin has been either ignored or stipulated arbitrarily, clinical anticancer activity has been uncovered. Lissoni’s work shows an anticancer effect in a variety of solid tumors and his work has been confirmed by others for melanoma and renal cell carcinoma. In many of these trials, meaningful clinical benefit, as well as antitumor activity, has been demonstrated.

It will be essential to the ultimate determination of melatonin’s place in cancer therapy to determine the circadian schedule that optimizes its medical benefit. Such clinical studies must employ a double-blind, placebo-controlled comparison among times of day for melatonin treatment, alone and in combination with surgery, radiation, chemotherapy, and/or biological therapies. Measures of quality of life, fatigue, the latency timing, quality and quantity of daily sleep, and the timing and intensity of daily activity should be assessed, along with melatonin’s anticancer activity, in each of these studies. Without chronobiologically adequate clinical studies, the use of melatonin will continue to depend upon belief and opinion rather than upon knowledge and understanding.