Chronotherapy: a noteworthy focal point in the treatment of cancer?

Abstract

In mammalian systems including humans, DNA synthesis, cell cycle and mitotic index are circadian in nature. Disrupted circadian clock leads to disturbed cellular rhythms, metabolism and hormonal balance and is noticeably accountable for the uncontrolled cell division ultimately leading to cancer. About a decade ago, there are fewer evidences on the role of biological clock on tumorigenesis. Currently, a relationship between shift work and cancer, distinctively breast cancer in women and prostate cancer in men, distraction of sleep–wake cycles and augmentation of cancer development, oncostatic effects of melatonin (the internal zeitgeber of circadian system), bidirectional relationships of circadian and immune systems, the prospect of clock genes as tumour suppressors, inaccurate temporal management of oxidative stress and genotoxicity have been recounted, making the crucial role of circadian clock in carcinogenesis. This review critically evaluates present knowledge on circadian rhythms in relation to cancer and its management. The accumulating and coercing evidences could be valuable in formulating the rhythm-based therapy as a remarkable focal point in the management of cancer.

Keywords:

• chronotherapy
• cell cycle clocks
• circadian
• cancer
• chronomodulation

Acknowledgements

Visiting Professorship to PS (at Department of Molecular Medicine, University of Malaya) is thankfully acknowledged. Financial assistance to OHH (RP017-13HTM and HIR-MOHE H-20001-00-E000009) is gratefully acknowledged.