Circadian Regulation of Drug Responses: Toward Sex-Specific and Personalized Chronotherapy

The Annual Review of Pharmacology and Toxicology, Journal Year: 2023, Volume and Issue: 64(1), P. 89 - 114

Published: Sept. 19, 2023

Today's challenge for precision medicine involves the integration of impact molecular clocks on drug pharmacokinetics, toxicity, and efficacy toward personalized chronotherapy. Meaningful improvements tolerability and/or medications through proper administration timing have been confirmed over past decade immunotherapy chemotherapy against cancer, as well commonly used pharmacological agents in cardiovascular, metabolic, inflammatory, neurological conditions. Experimental human studies recently revealed sexually dimorphic circadian responses. Dedicated randomized clinical trials should now aim to issue recommendations daily medical practice, integrating innovative technologies remote longitudinal monitoring metrics, statistical prediction clock function from single-timepoint biopsies, multiscale biorhythmic mathematical modelling. Importantly, chronofit patients with a robust function, who would benefit most chronotherapy, need be identified. Conversely, nonchronofit could emerging class chronobiotics targeting clock.

Language: Английский

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Shaping the future of precision oncology: Integrating circadian medicine and mathematical models for personalized cancer treatment

Current Opinion in Systems Biology, Journal Year: 2024, Volume and Issue: 37, P. 100506 - 100506

Published: Feb. 29, 2024

The growing numbers of cancer cases represent a medical and societal burden worldwide. More than half all patients are treated with chemotherapy. Yet, chemotherapeutic drugs kill not only cells, but also healthy tissue, causing massive adverse side effects. Recent research on circadian medicine suggests that side-effects can be reduced, treatment efficacy increased, by considering the biological clock patients. Integrating profiles molecular markers in personalized mathematical models simulate individual dynamics drug uptake, action cellular response to This requires advanced computational tools balance prediction quality overfitting. Personalized will eventually lead an optimal alignment timing inner patient, reducing effects, increasing enhancing patient well-being.

Language: Английский

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Time matters: chrono-pharmacotherapy as precision medicine

Asia-Pacific Journal of Pharmacotherapy & Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

The circadian clock and its inherent rhythms serve as the foundation for regulating many of body’s vital processes. Recent advances in medicine have leveraged these natural cycles through chronotherapy, practice timing drug administration to align with body's internal clock, enhance treatment outcomes. Endogenous clocks not only dictate physiological but also influence how drugs are absorbed, distributed, metabolized, excreted, thereby affecting both their therapeutic efficacy potential toxicity. When disrupted, resulting imbalance has been linked a range disorders, such cancer cardiovascular diseases, highlighting growing need time-sensitive strategies. Technological breakthroughs, including wearable sensors, digital health platforms, sophisticated machine learning techniques, now allow continuous, real-time monitoring biomarkers, which turn helps optimize regimens. In oncology, example, synchronizing chemotherapy, therapy, immunotherapy anti-inflammatory patient’s cycle shown effectiveness improve tolerability. Moreover, observed sex-based differences responses emphasize importance tailoring individual patient profiles. Emerging research is focusing on directly targeting molecular components, showing treating metabolic oncological conditions. However, fully integrating chronopharmacology into clinical will require development standardized protocols, regulatory backing, large-scale trials that incorporate biomarkers. Ultimately, merging biology strategies promises efficacy, minimize side effects, Future studies must address inter-individual variability, sex differences, misalignment harness chronotherapy’s personalized medicine.

Language: Английский

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Personalization of Cancer Treatment: Exploring the Role of Chronotherapy in Immune Checkpoint Inhibitor Efficacy

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 732 - 732

Published: Feb. 21, 2025

In the era of precision medicine, mounting evidence suggests that time therapy administration, or chronotherapy, has a great impact on treatment outcomes. Chronotherapy involves planning timing by considering circadian rhythms, which are 24 h oscillations in behavior and physiology driven synchronized molecular clocks throughout body. The value chronotherapy cancer is currently under investigation, notably effects efficacy side effects. Immune checkpoint inhibitor (ICI) promising treatment. However, many patients still experience disease progression need to stop early due There accumulating day at ICI administered can have substantial effect efficacy. Thus, it important investigate intersections this review, we provide brief overview rhythms context immunity cancer. Additionally, outline current applications for We synthesize 29 studies conducted date examine time-of-day administration therapy, its associated effects, sex differences both also discuss potential mechanisms underlying these observed results. Finally, highlight challenges area future directions research, including chronotherapeutic personalized medicine approach tailors individual patients’ rhythms.

Language: Английский

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Circadian rhythm-based cancer therapy in randomised clinical trials

Expert Review of Anticancer Therapy, Journal Year: 2023, Volume and Issue: 24(1-2), P. 29 - 39

Published: Dec. 21, 2023

Since the 2017 Nobel Prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology number anatomical sites interest this field increasing. This observation line with clinical evidence provided by trials on head neck, lung, colorectal cervical cancers, well presently ongoing chronotherapy breast brain cancers.

Language: Английский

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