Chronobiology and Chronomedicine

Royal Society of Chemistry eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

Circadian rhythms have been shown to be ubiquitous and critically important in the experimental laboratory, accounting for difference between life death response identical stimulus. The partly endogenous nature of circadian has well documented methods their characterisation developed enabling cellular molecular mechanisms understood. Chronobiology Chronomedicine aims provide a review these underlying illustrate role brain’s suprachiasmatic nuclei ‘pace-making’ process effects caused by ‘clock genes’ present almost all cells. Beyond involved, book discusses relationship body systems, disease, proper function; particular, how disruption rhythm is associated with ill health disease status from observations made at organismic level. organised an ideal introduction postgraduate various fields, reviewing developments outlining show depth breadth chronobiology chronomedicine, as invaluable companion researchers healthcare professionals working field interest developing novel therapeutic approaches.

Language: Английский

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Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 4, 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting and activity-rest coordinating the behavior physiology all organs for whole-body homeostasis. Acute disruption may lead to transient discomfort, whereas long-term irregular will result in dysfunction organism, therefore increasing risks numerous diseases especially cancers. Indeed, both epidemiological experimental evidence has demonstrated intrinsic link between dysregulated cancer. Accordingly, rapidly understanding molecular mechanisms rhythms opening new options cancer therapy, possibly by modulating clock. In this review, we first describe general regulators their functions on addition, provide insights into underlying how several types (including sleep-wake, eating-fasting, activity-rest) can drive progression, which expand our development from clock perspective. Moreover, also summarize potential applications treatment, optional therapeutic strategy patients.

Language: Английский

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Toxicity and efficacy of chronomodulated chemotherapy: a systematic review

The Lancet Oncology, Journal Year: 2022, Volume and Issue: 23(3), P. e129 - e143

Published: Feb. 28, 2022

Language: Английский

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Rhythm is essential: Unraveling the relation between the circadian clock and cancer

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104632 - 104632

Published: Jan. 1, 2025

Language: Английский

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Circadian rhythm disruption by PARP inhibitors correlates with treatment toxicity in patients with ovarian cancer and is a predictor of side effects

EBioMedicine, Journal Year: 2025, Volume and Issue: unknown, P. 105764 - 105764

Published: May 1, 2025

Ovarian cancer is among the most lethal malignancies in women. The advent of PARP inhibitors (PARPi) has improved outcomes. However, treatment-related toxicity remains a critical challenge, impacting patient quality life and treatment adherence. In circadian sub-study MAMOC trial-a double-blind, phase III study-42 patients (FIGO stage IIIA-IV) were randomised 2:1 ratio to receive rucaparib or placebo. subset these patients, we performed differential gene expression rhythmicity analysis on up 800 genes, including clock clock-controlled genes. Machine learning algorithms mathematical modelling employed simulate patient-specific profiles explore correlations between patterns side effects. Our revealed significant disruptions rhythms, specifically core genes BMAL1 PER2, following treatment. These strongly correlated with severity frequency effects, nausea fatigue, displaying opposite trends placebo rucaparib-treated groups. K-means clustering successfully distinguished from those receiving based profiles. addition, therapy also altered several SIRT1, BRCA1, BRCA2, TP53. Notably, our data suggest that individual differences rhythms may lead distinct 24-h patients. findings rhythm dysregulation contribute PARPi therapy. Aligning timing could mitigate adverse improve This study was funded by Dr. Rolf Schwiete Stiftung MSH Medical School Hamburg, Germany. trial (ClinicalTrials.gov: NCT04227522) Clovis Oncology, United States.

Language: Английский

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Wearable technology and systems modeling for personalized chronotherapy

Current Opinion in Systems Biology, Journal Year: 2020, Volume and Issue: 21, P. 9 - 15

Published: June 1, 2020

Chronotherapy is a pharmaceutical intervention that considers the patient's internal circadian time to adjust dosing time. Although it can dramatically improve drug efficacy and reduce toxicity, large variability in across within individuals has prevented chronotherapies from progressing beyond clinical trials. To translate chronotherapy developments into real-world outpatient scenario, personalized characterization analysis of essential. Here, we describe recent advances wearable technology enable real-time high-resolution tracking ultradian rhythms. We discuss how integrating data platforms including systems modeling machine learning pave way toward adaptive chronotherapy.

Language: Английский

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A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer

Computational and Structural Biotechnology Journal, Journal Year: 2021, Volume and Issue: 19, P. 5170 - 5183

Published: Jan. 1, 2021

Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of timing using novel mathematical model irinotecan cellular pharmacokinetics and –dynamics linked to representation the core clock predict toxicity colorectal cancer (CRC) model. The is fitted three different scenarios: mouse liver, where metabolism mainly occurs, two human cell lines representing an vitro experimental system for progression. Our successfully recapitulates quantitative circadian datasets mRNA protein expression together with timing-dependent cytotoxicity data. also discriminates time-dependent between cells, suggesting that can be optimized according their clock. results show degradation mediating activation, as well oscillation death rate play important role variations toxicity. In future, this used support personalized scheduling by predicting optimal based on patient's gene profile.

Language: Английский

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Radiation chronotherapy—clinical impact of treatment time-of-day: a systematic review

Journal of Neuro-Oncology, Journal Year: 2019, Volume and Issue: 145(3), P. 415 - 427

Published: Nov. 15, 2019

Language: Английский

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Personalized Chronomodulated 5‐Fluorouracil Treatment: A Physiologically‐Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy

Clinical Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 115(6), P. 1282 - 1292

Published: Jan. 24, 2024

The discovery of circadian clock genes greatly amplified the study diurnal variations impacting cancer therapy, transforming it into a rapidly growing field research. Especially, use chronomodulated treatment with 5‐fluorouracil (5‐FU) has gained significance. Studies indicate high interindividual variability (IIV) in dihydropyrimidine dehydrogenase (DPD) activity – key enzyme for 5‐FU metabolism. However, influence individual DPD chronotypes on therapy remains unclear and warrants further investigation. To optimize precision dosing 5‐FU, this aims to: (i) build physiologically‐based pharmacokinetic (PBPK) models uracil, their metabolites, (ii) assess impact variation activity, (iii) estimate chronotypes, (iv) personalize infusion rates based patient's chronotype. Whole‐body PBPK were developed PK‐Sim (R) MoBi . Sinusoidal functions used to incorporate as well from DPYD mRNA expression or enzymatic activity. Four whole‐body metabolites established utilizing data 41 10 publicly available uracil studies. IIV was assessed personalized administrations achieve comparable peak plasma concentrations, exposure, constant levels via “noise cancellation” infusion. capture extent can help investigate individualized through testing alternative strategies.

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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