Time Recall; Future Concept of Chronomodulating Chemotherapy for Cancer
Paul Zarogoulidis, Kaid Darwiche, Haidong Huang, Dionysis Spyratos, Lonny Yarmus, Qiang Li, Stylianos Kakolyris, Konstantinos Syrigos and Konstantinos Zarogoulidis
Affiliation: Pulmonary Department, G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki. Thessaloniki, Greece.
The human metabolism is regulated by our internal clock; the circadian rhythm (24h-25h). There are several
factors included in the regulatory pathway such as; genes (PER1-3), (CRY1-2), TIM hormones (cortisol, catecholamines,
melatonin and insulin) drugs, enzymes, sleep disorders and diseases. Each one contributes in a different degree and in order
to enhance the therapeutic result; we should include these factors into clusters instead of targeting each factor one by
one. Malignances deregulate gene-protein expression/production, enzyme production, and in addition they induce fatigue,
insomnia, stress and sleep disorders. All these factors finally contribute in minimizing the efficiency of chemotherapy
treatment and quality of life. In addition, the circadian rhythm disruption induces tumor genesis, stress, and downregulates
the defense and repair mechanisms of the human body. In the current mini review the underlying mechanism of
the circadian rhythm is provided, along with the influence of sleep disturbances in cancer patient therapy. A proposal is
presented to divide circadian rhythm and sleep disturbances into two major clusters with different management, however;
with a common target to improve treatment efficiency and quality of life. Finally, a chrono-chemotherapy administration
model is proposed in order to have less chemotherapy side effects.
Keywords: Chronomodulation, Cancer, Chemotherapy, Circadian rhythm, Sleep disorders.
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