Circadian Rhythms in Cancer: Mechanistic Insights, Chronotherapeutic Strategies, and Translational Challenges

📖 Top 20% JournalSep 18, 2025Annals of surgical oncology

Body Clock Patterns in Cancer: How They Work, Timing Treatments, and Challenges for Patient Care

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Abstract

Circadian rhythm disruptions are increasingly linked to tumorigenesis and treatment resistance.

Core circadian regulators like BMAL1, PER, and CRY interact with oncogenic pathways such as p53, MYC, and PI3K/AKT.
Preclinical studies show that the effectiveness and toxicity of cancer treatments can vary based on the time of day.
Clinical translation of these findings is limited by varied circadian patterns among patients and logistical challenges.
Emerging technologies, including organ-on-a-chip systems and wearable monitoring devices, may enable personalized treatment schedules.
Validation of these innovative approaches is still needed across different patient populations and cancer types.

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Circadian rhythms orchestrate essential physiological functions, including cell proliferation, DNA repair, immune surveillance, and metabolism, and their disruption has been increasingly associated with tumorigenesis, disease progression, and treatment resistance. This review synthesizes recent mechanistic insights into how core circadian regulators-such as BMAL1, PER, and CRY-interact with key oncogenic pathways, including p53, MYC, and PI3K/AKT, to shape tumor behavior. Preclinical studies demonstrate time-of-day-dependent variation in the efficacy and toxicity of chemotherapy, radiotherapy, and targeted therapies; however, clinical translation remains limited, constrained by heterogeneous circadian phenotypes, logistical challenges, and the absence of standardized rhythmic biomarkers. We critically evaluate emerging technologies, such as organ-on-a-chip systems, wearable circadian monitoring devices, and artificial intelligence (AI)-guided dosing models, that hold promise for enabling personalized chronotherapy. Despite growing interest, substantial gaps remain in validating these approaches across diverse patient populations and tumor types. We propose that advancing chronotherapeutic strategies will require robust rhythm quantification tools, integration of multi-omics analyses, and circadian-aware clinical trial designs. Ultimately, aligning treatment with biological time could unlock new therapeutic windows and improve cancer outcomes, but successful implementation will depend on bridging molecular chronobiology with precision oncology.

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