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

Bibliometric analysis of global research status and trends of circadian rhythms in cancer from 2004 to 2024 DOI
Zhihong Chen, Shitao Jiang, Y. Liu

et al.

Chronobiology International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Jan. 31, 2025

Research linking circadian dysregulation to cancer development has received increasing attention recently. However, a comprehensive understanding of research hotspots and trends in this area remains limited. International studies on the rhythms were retrieved downloaded from Web Science database. Bibliometric analysis visualization performed using VOSviewer, CiteSpace, HistCite. Three thousand three hundred eighteen English articles 2004 2024 screened evaluated. The increase publications citations reflected rapid expansion field. Scholars institutions United States have relatively high academic productivity impact. Chronobiology is most popular journal. Key clustering identified six themes: biochemistry molecular biology, physiology immunomodulation, night shift work health effects, physiological mental health, tumor therapy research, oxidative stress cancer-related mechanisms. Keyword burst regulation cells microenvironment as frontiers. role immunotherapy was current hotspot by reference co-citation analysis. This study reveals status predicts future trends. These findings provide new ideas for developing novel prevention treatment strategies.

Language: Английский

Citations

0
Device Development: The Future DOI

Benjamin D. Ferguson,

Hari Nathan

Published: Jan. 1, 2025

Language: Английский

Citations

0
Translating around the clock: Multi-level regulation of post-transcriptional processes by the circadian clock DOI

Amber A. Parnell,

Aliza K. De Nobrega, Lisa C. Lyons

et al.

Cellular Signalling, Journal Year: 2020, Volume and Issue: 80, P. 109904 - 109904

Published: Dec. 25, 2020

Language: Английский

Citations

30
MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer DOI Open Access
Jamison B. Burchett, Amelia Clark, Brian J. Altman

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7761 - 7761

Published: July 20, 2021

The MYC oncoprotein and its family members N-MYC L-MYC are known to drive a wide variety of human cancers. Emerging evidence suggests that has bi-directional relationship with the molecular clock in cancer. is responsible for circadian (~24 h) rhythms most eukaryotic cells organisms, as mechanism adapt light/dark cycles. Disruption rhythms, such through shift work, may serve risk factor cancer, but connections oncogenic drivers were previously not well understood. In this review, we examine recent cancer can disrupt clock; conversely, disruption deregulate elevate MYC. Since control many same processes, then consider competition between several select aspects tumor biology, including chromatin state, global transcriptional profile, metabolic rewiring, immune infiltrate tumor. Finally, discuss how be monitored or diagnosed tumors, inhibition could potentially restore function. Further study reveal unsuspected vulnerabilities which lead new treatment strategies.

Language: Английский

Citations

25
Personalized Chronomodulated 5‐Fluorouracil Treatment: A Physiologically‐Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy DOI Creative Commons

Fatima Zahra Marok,

Jan‐Georg Wojtyniak, Dominik Selzer

et al.

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

Citations

3
Exploring the link between chronobiology and drug delivery: effects on cancer therapy DOI

Tânia Albuquerque,

Ana R. Neves, Telma Quintela

et al.

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

Published: July 2, 2021

Language: Английский

Citations

21
Efficacy and safety of chronomodulated irinotecan, oxaliplatin, 5‐fluorouracil and leucovorin combination as first‐ or second‐line treatment against metastatic colorectal cancer: Results from the International EORTC 05011 Trial DOI Creative Commons
Pasquale F. Innominato, Abdoulaye Karaboué,

C. Focan

et al.

International Journal of Cancer, Journal Year: 2020, Volume and Issue: 148(10), P. 2512 - 2521

Published: Dec. 3, 2020

Abstract The triplet combination of irinotecan, oxaliplatin and fluorouracil is an active frontline regimen in metastatic colorectal cancer, but scarce data exist on its use as salvage treatment. We aimed at assessing safety efficacy profiles with circadian‐based administration (chronoIFLO5) either first‐ or second‐line treatment, within the time‐finding EORTC 05011 trial. Five‐day chronoIFLO5 was administered every 3 weeks patients PS 0, 1 2. It consisted chronomodulated irinotecan (180 mg/sqm), (80 mg/sqm) fluorouracil‐leucovorin (2800 1200 mg/sqm, respectively). For our study, toxicity antitumour activity were evaluated separately settings. Primary endpoints included Grade 3‐4 rates, best objective response rate (ORR), progression‐free survival (PFS) overall (OS). One‐hundred forty‐nine 44 treated first‐line settings, respectively, a total 1138 cycles median relative dose intensities about 90%. Demographics comparable two groups. Thirty‐six (24.7%) 10 (22.2%) experienced least one episode severe first line second line, respectively. Frontline yielded ORR 62.3% [95% CI: 54.2‐70.4] resulted PFS OS 8.7 months [7.5‐9.9] 19.9 [15.4‐24.5]. Corresponding figures 37.5% [22.5‐52.5], 6.7 [4.8‐8.9] 16.3 [11.8‐20.8]. International prospective evaluation revealed favourable chronoIFLO5, both treatment against cancer. In particular, encouraging observed, limited haematological toxicity.

Language: Английский

Citations

21
Clock at the Core of Cancer Development DOI Creative Commons
Sonal A. Patel, Roman V. Kondratov

Biology, Journal Year: 2021, Volume and Issue: 10(2), P. 150 - 150

Published: Feb. 14, 2021

To synchronize various biological processes with the day and night cycle, most organisms have developed circadian clocks. This evolutionarily conserved system is important in temporal regulation of behavior, physiology metabolism. Multiple pathological changes associated disruption support importance clocks mammals. Emerging links revealed interplay between signaling networks cancer. Understanding cross-talk clock tumorigenesis imperative for its prevention, management development effective treatment options. In this review, we summarize role one metabolic pathway, insulin/IGF1/PI3K/mTOR signaling, how dysregulation pathway could lead to uncontrolled cancer cell proliferation growth. Targeting rhythms either recently discovered pharmaceutical agents or through environmental cues a new direction chronotherapy. Combining approach traditional methods, such as radiation, chemotherapy developed, immunotherapy, may improve tumor response, while simultaneously minimizing adverse effects commonly therapies.

Language: Английский

Citations

20
Controlled Release Technologies for Chronotherapy: Current Status and Future Perspectives DOI
Bhavana Bhat, Chetan Hasmukh Mehta, Akhil Suresh

et al.

Current Pharmaceutical Design, Journal Year: 2023, Volume and Issue: 29(14), P. 1069 - 1091

Published: April 1, 2023

Abstract: The expression “as sure as night follows a day” emulates those certain cycles in the environment that are always stable. Circadian rhythms group of processes occur within body synchronisation with external factors 24 h cycle. Changes lifestyle and work shifts have disrupted these stable rhythms, which is leading cause diseases. Associations between biological clocks diseases abundant. However, it also known drugs more efficiently minimum toxicity when given during particular phase circadian Chronotherapeutics focuses on treating according to endogenous mediate xenobiotic metabolism drug response at cellular level. Therefore, treatment show aggravation symptoms time highly beneficial by chronotherapy. In this article, we emphasised how changes caused chronotherapeutic approaches such controlled release technologies can be better option for manipulations seem influence all types disease conditions.

Language: Английский

Citations

7
Coupling between the cell cycle and the circadian clock: Lessons from computational modelling and consequences for cancer chronotherapy DOI
Didier Gonze

Current Opinion in Systems Biology, Journal Year: 2024, Volume and Issue: 37, P. 100507 - 100507

Published: Feb. 2, 2024

Language: Английский

Citations

2