Circadian-system alterations during cancer processes: A review

Abstract

Murine and human data have indicated that tumors and tumor-bearing hosts may exhibit nearly normal or markedly altered circadian rhythms. Amplitude damping, phase shifts, and/or period (t) change, including appearance of ultradian rhythms (with t F 20 hr) usually become more prominent at late stages of cancer development. The extent of rhythm alterations also varies according to tumor type, growth rate and level of differentiation. While ''group chronotherapy,'' i.e., administration of the same chronomodulated schedule to cancer patients, has increased chemotherapy efficacy and/or tolerability, cancer patients' individual circadian rhythms now need to be explored on a large scale, in order to estimate the incidence of cancer-associated circadian-system alterations and to understand the underlying mechanisms. Correlations between such alterations and patient outcome must be established in order to specify the need for individualized chronomodulated delivery schedules and/or specific rhythmoriented therapy, especially in patients with circadian-system disturbances. Int. J. Cancer, 70:241-247, 1997.r 1997 Wiley-Liss, Inc.Biological functions are modulated by rhythms along several periodic time-scales, i.e., ultradian (with a period, t, shorter than 20 hr), circadian (t approx. 24 hr) or infradian (t . 28 hr). Circadian rhythms are endogenous, genetically based, and coordinated by at least one biological clock, the supra-chiasmatic nucleus (SCN). The circadian periodicity of the SCN can be calibrated by environmental cycles with a t approaching 24 hr. The 24-hr light-dark cycle plays such a role, via specific neuronal pathways and neuromediators, and via darkness-induced secretion of melatonin.

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

“…Indeed, in the presence of a tumour, daily activity levels of mice decreased over time which is in line with clinical reports of cancer patients (Mormont and Levi, 1997;Mormont et al, 2000). It is not clear what mechanism induces the reduction in activity in cachectic cancer patients.…”

“…Chevalier et al (2003) reported that patients with advanced colorectal cancer showed less contrast between day time and night time activity (nocturnal sleep) . Individual activity patterns have even been suggested to be predictive of the patients' survival, tumour response and quality of life (Mormont and Levi, 1997;Mormont et al, 2000). The possibility of a tumour-induced disturbance in diurnal activity patterns is supported by our data, indicating a tumour-related shift in activity from the dark to the light period.…”

Clock-cancer connection in non-Hodgkin’s lymphoma

“…A disruption of the circadian cycle may result in disordered immune responses such as aberrant immune cell trafficking and abnormal cell proliferation cycles [30][31][32]. Sleep disorders, which result in an altered circadian rhythm, have been shown to affect the expression of the hypothalamic-pituitary-adrenal (HPA) axis.…”

Identification of Circadian Determinants of Cancer Chronotherapy through In Vitro Chronopharmacology and Mathematical Modeling

“…Indeed, up-to-severalfold changes in treatment tolerability and/or efficacy were found according to dosing time for 40 anticancer drugs in rodents (2). Moreover, the administration of anticancer agents at the circadian time when they were the safest also achieved best efficacy both in rodents (4) and in cancer patients (5)(6)(7)(8). Large intersubject differences in CTS further need to be taken into account for the personalization of circadian delivery of cancer treatments (9,10).…”