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Clocking cancer: the circadian clock as a target in cancer therapy

Abstract

Disruption of the cellular pathway modulating endogenous 24-h rhythms, referred to as “the circadian clock”, has been recently proven to be associated with cancer risk, development, and progression. This pathway operates through a complex network of transcription-translation feedback loops generated by a set of interplaying proteins. The expression of core circadian clock genes is frequently dysregulated in human tumors; however, the specific effects and underlying mechanisms seem to vary depending on the cancer types and are not fully understood. In addition, specific oncogenes may differentially induce the dysregulation of the circadian clock in tumors. Pharmacological modulation of clock components has been shown to result in specific lethality in certain types of cancer cells, and thus holds great promise as a novel anti-cancer therapeutic approach. Here we present an overview of the rationale and current evidence for targeting the clock in cancer treatment.

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Fig. 1: The mammalian circadian clock.
Fig. 2: Circadian clock components and cancer hallmarks.

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Acknowledgements

We thank Tsuyoshi Hirota and Jamie Cope for the critical reading of the manuscript.

Funding

Partly supported by the USC/Norris Translational Team Accelerator Project Initiative, the National Cancer Institute (grant numbers P30CA014089, UG1CA180830, R01CA23866201), the National Institute of Neurological Disorders and Stroke (grant number 1F31NS120654-01), the Gloria Borges WunderGlo Foundation, the Gene Gregg Pancreas Research Fund, and the Victoria Wilson Research Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute of the National Institutes of Health.

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Correspondence to Heinz-Josef Lenz.

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SAK serves on the board of Synchronicity Pharma and received research support from the company. Other authors declare no potential competing interests.

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Battaglin, F., Chan, P., Pan, Y. et al. Clocking cancer: the circadian clock as a target in cancer therapy. Oncogene 40, 3187–3200 (2021). https://doi.org/10.1038/s41388-021-01778-6

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