Chrono-Pharmacology for Cancer: Harnessing Circadian Regulations of the Cell Cycle and Immune Response Dynamics for Precision Therapy

📖 Top 20% JournalNov 20, 2025ACS pharmacology & translational science

Using Body Clock Timing of Cell Growth and Immune Changes to Improve Cancer Treatment

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Abstract

Disruption of circadian rhythms and the cell cycle may significantly contribute to tumorigenesis and cancer progression.

Circadian rhythms regulate cell proliferation by controlling key cell cycle regulators like WEE1, p21, and MYC.
The dysregulation of circadian clock components can arise from genetic or environmental factors.
Alterations in the synchronization between the circadian clock and the cell cycle are linked to decreased DNA repair fidelity and stability of oncogenes.
Chrono-pharmacology suggests that the effectiveness and side effects of anticancer drugs vary depending on the time of day.
Certain drugs, including HSP90 inhibitors and topoisomerase inhibitors, exhibit therapeutic activities regulated by circadian control.
The circadian influence also impacts the tumor microenvironment and antitumor immunity, indicating potential for novel treatment strategies.

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The circadian rhythms and cell cycle are closely interlinked, creating a fundamental regulatory axis vital for tissue homeostasis, which is frequently dysregulated in cancers. The circadian apparatus, which is regulated by the core clock components (BMAL1, CLOCK, PER, and CRY in mammals), establishes temporal order on cell proliferation by rhythmically regulating important cell cycle regulators such as WEE1, p21, and the oncogene MYC. This is frequently accomplished through overlapped signaling nodes that include particular kinases and ubiquitin ligases (e.g., FBXW7). Mounting evidence implicates disruption of this circadian clock-cell cycle synchrony, arising from genetic or environmental factors, as a significant contributor to tumorigenesis and progression via impacts on DNA repair fidelity, oncogene stability, and tumor suppressor pathways. This review critically evaluates the new concept of chrono-pharmacology for cancer, focusing on the substantial effects and side effects of different anticancer drugs that depend on the time-of-day efficacy. We discussed some interesting examples, like HSP90 inhibitors (ganetespib), HDAC inhibitors (quisinostat), topoisomerase inhibitors (doxorubicin), and BCL-2 family antagonists (Obatoclax, TW-37), whose therapeutic activities are tightly regulated by circadian control over their molecular targets, pharmacokinetic processes, and downstream physiological pathways. Furthermore, the circadian influence extends to the tumor microenvironment and antitumor immunity, suggesting novel chrono-immunotherapy approaches. By putting together the molecular bases of these temporal dynamics, this review underscores the significant potential of chronotherapythe timed administration of drugs to improve cancer treatment by enhancing therapeutic indices and paving the way for personalized, temporally optimized oncology strategies.

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