The Circadian Clock in Cancer Development and Therapy - Progress in Molecular Biology and Translational Science - page 259

6. CONCLUSIONS

The rate of cancer continues to rise as more people live to an old age and
changes in lifestyle affect more developing countries. 482 Cancer is usually not
detected at the early stage due to the absence of any obvious symptoms. 191,483
However, the fact that only 5-10% of all cancers diagnosed are caused by
inherited genetic mutations suggests that an unhealthy lifestyle is the major
risk factor for cancer. Therefore, cancer is preventable. 401 Mounting evidence
obtained from recent studies suggests that disruption of endogenous circadian
homeostasis is a novel and independent risk factor for cancer. In addition, as a
master regulator of mammalian physiology, disruption of the clock likely
manifests cancer development and progression induced by previously identi-
fied exogenous and endogenous cancer risk factors including diet choices,
tobacco and alcohol usage, viral infection, air pollutions, aging, endocrine dys-
function, metabolic syndromes, and immune deficiencies. 484,485 Although
still at the initial stage, recent advancements strongly suggest that both tumor
suppression and response to anticancer treatments are clock-controlled phys-
iological functions in vivo . Therefore, the mammalian circadian clock provides
an invaluable and exciting system to study the mechanism of cancer and anti-
cancer chronotherapy at the molecular, cellular, tissue, organ, and organismal
levels in vivo . Such studies will have a significant impact on human health in
the future by improving both cancer prevention and treatment.

ACKNOWLEDGMENTS
The authors would like to thank D. D. Moore for input in preparing the manuscript. This
work is supported by the grants from USDA/ARS (6250-51000-055) and NIH/NCI (R01
CA137019-01A) to L. F. and the training grant award from NIH/NIDDK to N. M. K.
(5T32DK007696-20).

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