Modeling the Circadian Control of the Cell Cycle and Its Consequences for Cancer Chronotherapy

Biology, Journal Year: 2023, Volume and Issue: 12(4), P. 612 - 612

Published: April 18, 2023

The mammalian cell cycle is governed by a network of cyclin/Cdk complexes which signal the progression into successive phases division cycle. Once coupled to circadian clock, this produces oscillations with 24 h period such that each phase synchronized day-night Here, we use computational model for clock control investigate entrainment in population cells characterized some variability kinetic parameters. Our numerical simulations showed successful and synchronization are only possible sufficient amplitude an autonomous close h. Cellular heterogeneity, however, introduces cells. Many cancer have disrupted or compromised control. In these conditions, runs independently leading lack When coupling weak, largely impacted, but maintain tendency divide at specific times day. These differential features between healthy can be exploited optimize timing anti-cancer drug administration order minimize their toxicity maximize efficacy. We then used our simulate chronotherapeutic treatments predict optimal drugs targeting Although qualitative, highlights need better characterize cellular heterogeneity populations as well consequences design chronopharmacological protocols.

Language: Английский

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Recent Advances in Chronotherapy Targeting Respiratory Diseases

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(12), P. 2008 - 2008

Published: Nov. 25, 2021

Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is natural biological process where our bodily functions align with the 24 h oscillation (sleep–wake cycle) are controlled by clock protein/gene. Disruption could alter normal lung function. Chronotherapy type therapy provided at specific time intervals based on an individual’s rhythm. This would allow drug show optimum action, thereby modulate its pharmacokinetics lessen unwanted or unintended effects. In this review, we deliberated recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.

Language: Английский

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Chronobiologie in der Onkologie: Onkologische Therapien am besten zur individuell optimalen Tageszeit

Deutsches Ärzteblatt, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

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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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Enhanced Circadian Phase Tracking: A 5-h DLMO Sampling Protocol Using Wearable Data

Journal of Biological Rhythms, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Circadian medicine aims to leverage the body’s internal clock develop safer and more effective therapeutics. Traditionally, biological time has been estimated using dim light melatonin onset (DLMO), a method that requires collecting saliva samples over long period under controlled conditions, ensure observation of DLMO, making it time-consuming labor-intensive. While some studies have mitigated this by reducing length sampling window, they significantly failed identify DLMO for shift workers. In study, we present framework reduces experiment workers just 5 h. This approach combines sleep-wake pattern data from wearable devices with mathematical model predict prospectively. Based on prediction, define targeted 5-h 3 h before 2 after DLMO. Testing 19 workers, successfully identified all participants, whereas traditional methods than 40% participants. required measuring 24 h, simplifying circadian phase measurements

Language: Английский

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Combining lineage correlations and a small molecule inhibitor to detect circadian control of the cell cycle.

iScience, Journal Year: 2025, Volume and Issue: 28(4), P. 112269 - 112269

Published: March 22, 2025

Chronotherapy offers an exciting possibility for improving cancer treatments by leveraging the influence of circadian clock on cell cycle. While several molecular interactions coupling two oscillators have been identified, whether they lead to emergent control cellular proliferation remains unclear. Using stochastic simulations, we demonstrate that established gene networks underlying are sufficient generate lineage correlations in cycle times, as observed single-cell microscopy data. The also create a 'therapeutic window' between and normal peaks can be leveraged chronotherapy. Surprisingly, our model predicts KL001, inhibitor, minimally affects population growth but significantly alters correlations. Our results suggest may not detectable measuring changes dynamics, combining measurements with KL001 treatment provide more sensitive approach detecting coupling.

Language: Английский

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Exploring the link between chronobiology and drug delivery: effects on cancer therapy

Journal of Molecular Medicine, Journal Year: 2021, Volume and Issue: 99(10), P. 1349 - 1371

Published: July 2, 2021

Language: Английский

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A Computational Analysis in a Cohort of Parkinson’s Disease Patients and Clock-Modified Colorectal Cancer Cells Reveals Common Expression Alterations in Clock-Regulated Genes

Cancers, Journal Year: 2021, Volume and Issue: 13(23), P. 5978 - 5978

Published: Nov. 28, 2021

Increasing evidence suggests a role for circadian dysregulation in prompting disease-related phenotypes mammals. Cancer and neurodegenerative disorders are two aging related diseases reported to be associated with disruption. In this study, we investigated possible effect of disruption Parkinson's disease (PD) colorectal cancer (CRC). We used high-throughput data sets retrieved from whole blood idiopathic PD (IPD) patients time course derived an vitro model CRC including the wildtype three core-clock knockout (KO) cell lines. Several gene expression alterations IPD resembled profiles KO cells. These include changes DBP, GBA, TEF, SNCA, SERPINA1 TGFB1. Notably, our results pointed network when compared healthy controls revealed variations profile PD-associated genes (e.g., HRAS GBA) upon genes. Our study characterizes at transcriptomic level following clock on common cellular pathways neurodegeneration immune system, energy metabolism RNA processing), it points significant influence overall survival colon several resulting analysis TUBB6, PAK6, SLC11A1).

Language: Английский

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A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients

Cancer and Metastasis Reviews, Journal Year: 2021, Volume and Issue: 40(4), P. 1055 - 1071

Published: Dec. 1, 2021

Abstract Sleep is a basic need that frequently set aside in modern societies. This leads to profound but complex physiological maladaptations the body commonly referred as circadian disruption, which recently has been characterized carcinogenic factor and reason for poor treatment outcomes, shortened survival, reduced quality of life cancer patients. As sleep physiology patients spans several disciplines including nursing science, neurology, oncology, molecular biology medical technology, there lack comprehensive integrated approaches deal with this serious growing issue at best fractionated understanding only part problem among researchers within each these segments. Here, we take multidisciplinary approach comprehensively review diagnosis impact disruption We discuss recent discoveries on regulation clock healthy malignant cells, neurological endocrine pathways controlling rhythmicity, their inputs outputs from organism. The benefits drawbacks various technologies, devices, instruments used assess function, well known consequences how can be corrected patients, will analyzed. throughout highlight extensive crosstalk between sleep, rhythms, metabolic involved malignancy identify current knowledge gaps barriers addressing By issues, hope provide foundation further research better more effective care future.

Language: Английский

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An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells

npj Systems Biology and Applications, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 23, 2023

Increasing evidence points to a role of the circadian clock in regulation cancer hallmarks with strong impact on understanding and treatment this disease. Anti-cancer can be personalized considering timing. Here we present new mathematical model based data from three colorectal cell lines core-clock knock-outs, which couples drug metabolism network, that allows determine toxicity profiles for given type. Moreover, integrates external Zeitgebers thus may used fine-tune by using factors, such as light, therefore, certain extent, help fitting endogenous rhythms patients defined clinic routine facilitating implementation time-dependent clinical practice.

Language: Английский

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