Application of Pharmacometrics of 5-Fluorouracil to Personalized Medicine: A Tool for Predicting Pharmacokinetic–Pharmacodynamic/Toxicodynamic Responses DOI Open Access
Shinji Kobuchi, Yukako Ιtο

Anticancer Research, Journal Year: 2020, Volume and Issue: 40(12), P. 6585 - 6597

Published: Dec. 1, 2020

Recently, therapeutic drug monitoring of 5-fluorouracil (5-FU), the key chemotherapeutic for colorectal cancer, has been applied in daily clinical practice and contributed towards improving outcomes. However, current dose modifications are based only on values area under plasma concentration–time profile, which simply calculated from 5-FU concentrations infusion periods. When dose-limiting toxicities occur, dosing is empirically reduced or discontinued, leading to treatment failure. To prevent this predictable failure obtain better outcomes, rational dosage-based strategies required 5-FU. Combining with a mathematical approach using pharmacokinetic– pharmacodynamic/toxicodynamic model expected help simulate time-course profiles efficacy drugs degree toxicity, thereby contributing setting individual patients. Therefore, facilitate pharmacometric modelling simulation techniques optimising oncology therapies, review focuses pharmacometrics approaches personalizing 5-FU-based chemotherapy.

Language: Английский

Chronobiology and Chronomedicine DOI Open Access
Germaine Cornélissen,

Kuniaki Otsuka,

Tsuyoshi Hirota

et al.

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

Citations

108

Circadian rhythms and cancers: the intrinsic links and therapeutic potentials DOI Creative Commons
Li Zhou, Zhe Zhang, Edouard C. Nice

et al.

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

Citations

91

Toxicity and efficacy of chronomodulated chemotherapy: a systematic review DOI
Markella I Printezi, Aoife B. Kilgallen, Marinde J. G. Bond

et al.

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

Published: Feb. 28, 2022

Language: Английский

Citations

61

Wearable technology and systems modeling for personalized chronotherapy DOI Creative Commons
Dae Wook Kim, Eder Zavala, Jae Kyoung Kim

et al.

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

Citations

43

A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer DOI Creative Commons
Janina Hesse, Julien Martinelli, Ouda Aboumanify

et al.

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

Citations

37

Radiation chronotherapy—clinical impact of treatment time-of-day: a systematic review DOI
Dorela D. Shuboni‐Mulligan, Ghislaı̀n Breton, Dee Dee Smart

et al.

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

Published: Nov. 15, 2019

Language: Английский

Citations

37

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

Courtney Leung,

Claude Gérard, Didier Gonze

et al.

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

Citations

11

Circadian regulation of sinoatrial nodal cell pacemaking function: Dissecting the roles of autonomic control, body temperature, and local circadian rhythmicity DOI Creative Commons
Li Pan, Jae Kyoung Kim

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(2), P. e1011907 - e1011907

Published: Feb. 26, 2024

Strong circadian (~24h) rhythms in heart rate (HR) are critical for flexible regulation of cardiac pacemaking function throughout the day. While this flexibility HR is sustained diverse conditions, it declines with age, accompanied by reduced maximal performance. The intricate involves orchestration autonomic nervous system (ANS), body temperature (CRBT), and local rhythmicity (LCR), which has not been fully understood. Here, we developed a mathematical model describing ANS, CRBT, LCR sinoatrial nodal cells (SANC) that accurately captures distinct patterns adult aged mice. Our underscores how alliance among achieves to cover wide range firing rates SANC, performance achieve rates, while preserving robustness generate rhythmic irrespective external conditions. Specifically, ANS dominates promoting SANC performance, CRBT act as primary secondary boosters, respectively, further enhance Disruption age results impaired but robustness. This unexpected outcome primarily attributed age-related reduction parasympathetic activities, maintains compromising flexibility. work sheds light on regulating time-of-day dysfunction, offering insights into novel therapeutic targets prevention treatment arrhythmias.

Language: Английский

Citations

4

Shaping the future of precision oncology: Integrating circadian medicine and mathematical models for personalized cancer treatment DOI Creative Commons
Janina Hesse, Nina Nelson, Angela Relógio

et al.

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

Citations

4

Rhythm is essential: Unraveling the relation between the circadian clock and cancer DOI
Olajumoke Ogunlusi, A. Ghosh, Mrinmoy Sarkar

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

0