Circadian genes CLOCK and BMAL1 in cancer: mechanistic insights and therapeutic strategies

Oct 20, 2025Journal of Zhejiang University. Science. B

How the body’s internal clock genes CLOCK and BMAL1 relate to cancer and possible treatments

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Circadian rhythm disruption is closely associated with the development of various malignancies.

Alterations in circadian gene expression profiles are observed in tumor tissues, indicating a dysfunction in core clock components.
Core clock proteins CLOCK and BMAL1 exhibit non-canonical oncogenic functions, including epigenetic regulation.
Dysregulation of circadian genes is linked to cell cycle control, DNA damage response, and metabolic reprogramming in cancer.
The tumor microenvironment (TME) may be remodeled by the effects of CLOCK/BMAL1 on cancer pathways.
Therapeutic strategies include chrononutritional interventions and chronopharmacological modulation aimed at optimizing treatment regimens.

AI simplified

The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably,demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies. CLOCK

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Circadian genes CLOCK and BMAL1 in cancer: mechanistic insights and therapeutic strategies

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief