Cancer metastasis mediated by circadian rhythm disruption: Molecular mechanisms to clinical significance and...

Area of Science:

• * Chronobiology and Cancer Metastasis Research
• * Molecular Biology and Immunology
• * Oncology and Therapeutics

Background:

• * The circadian rhythm, governed by core molecules like BMAL1, CLOCK, PERs, and CRYs, influences physiological processes over approximately 24 hours.
• * Disruptions to this biological clock are increasingly linked to cancer progression and metastasis.
• * Understanding these links is crucial for developing novel cancer treatment strategies.

Purpose of the Study:

• * To review the role of circadian rhythm disruption in promoting cancer metastasis.
• * To explore the mechanistic links between clock dysregulation and metastatic processes.
• * To highlight the therapeutic potential of targeting circadian rhythms in cancer.

Main Methods:

• * Comprehensive literature review of studies on circadian rhythm, cancer metastasis, and chronotherapy.
• * Analysis of molecular mechanisms linking clock genes to epithelial-mesenchymal transition, cancer stem cells, and immune surveillance.
• * Synthesis of evidence on therapeutic interventions targeting circadian pathways.

Main Results:

• * Circadian disruption promotes metastasis by altering extracellular matrix remodeling, increasing matrix stiffness, and creating a pro-metastatic niche.
• * Clock dysregulation impairs immune surveillance through T cell exhaustion, NK cell senescence, and pro-tumorigenic macrophage polarization.
• * Targeting core circadian molecules and chronotherapy show promise in preclinical and clinical settings.

Conclusions:

• * Circadian rhythm disruption acts as a key regulator of metastatic plasticity across various cancers.
• * A unifying model positions circadian disruption as a temporal gatekeeper in cancer metastasis.
• * Chronotherapeutic strategies targeting circadian rhythms offer a promising avenue for controlling cancer spread.