The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer

Area of Science:

• Oncology
• Chronobiology
• Cancer Biology

Background:

• Cancer is a complex disease influenced by the tumor microenvironment (TME).
• Temporal dynamics of tumors and circadian clock interactions are understudied.
• Circadian rhythms are increasingly linked to breast cancer risk, progression, and treatment.

Purpose of the Study:

• To review how circadian rhythms organize breast cancer biology via bidirectional interactions with the TME.
• To explore the role of circadian clocks in coordinating key cancer processes.
• To integrate insights on circadian timing, TME, and potential chronotherapeutics.

Main Methods:

• Literature review integrating research on circadian rhythms, breast cancer, TME, metabolism, immunology, and aging.
• Analysis of bidirectional interactions between circadian clocks and the TME components like the extracellular matrix.
• Examination of systemic effects of circadian disruption on cancer progression and immune surveillance.

Main Results:

• Circadian clocks regulate breast cancer proliferation, DNA repair, metabolism, and immune surveillance.
• Factors like aging, stress, and obesity disrupt circadian rhythms, accelerating breast cancer via feed-forward loops.
• The extracellular matrix (ECM) mediates bidirectional clock-TME control, influencing inflammation, stemness, and metastasis.
• Circadian rhythms dictate immune cell trafficking, creating windows for therapy.

Conclusions:

• Circadian timing is a unifying factor connecting cell-intrinsic programs with the breast TME.
• Dysfunctional circadian rhythms, exacerbated by lifestyle factors, promote breast cancer.
• Understanding these temporal dynamics opens avenues for chronotherapeutic strategies to improve breast cancer outcomes.