Deregulation of the circadian clock constitutes a significant factor in tumorigenesis: a clockwork cancer. Part II. In vivo studies

The uneventful progression through the cell cycle is closely associated with the rhythm set by the circadian clock machinery, with the S-phase of the cell cycle typically occurring at night. Presence of unrepaired DNA damage may reset the phase of the circadian clock, providing opportunities for damage assessment, repair and/or the induction of pro-apoptotic pathways. The core proteins of the circadian clock regulate directly or indirectly a significant number of genes coding for proteins involved in checkpoint transition, cell proliferation and programmed cell death. Disruption of the circadian rhythm may increase the risk for some multifactorial diseases and conditions, including glucose intolerance, cardiovascular disease and various common cancers. In patients with cancer, chronic circadian misalignment may stimulate the growth of tumours and may modify the outcomes of anticancer therapy. Knowledge about the role of physiological rhythms in human disease may contribute to the field of individualized medicine, specifically, in risk assessment and prognostication of the outcomes in patients with multifactorial disease.