A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer
| العنوان: | A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer |
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| المؤلفون: | Ouda Aboumanify, Angela Relógio, Julien Martinelli, Janina Hesse, Annabelle Ballesta |
| المساهمون: | Hamburg University of Applied Sciences [Hamburg], Humboldt University Of Berlin, Computational systems biology and optimization (Lifeware), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris-Saclay |
| المصدر: | Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 5170-5183 (2021) Computational and Structural Biotechnology Journal Computational and Structural Biotechnology Journal, 2021, 19, pp.5170-5183. ⟨10.1016/j.csbj.2021.08.051⟩ |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Drug, Colorectal cancer, media_common.quotation_subject, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], Circadian clock, Biophysics, Biochemistry, Structural Biology, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Genetics, medicine, Circadian rhythms, Circadian rhythm, Translational-transcriptional networks, ComputingMethodologies_COMPUTERGRAPHICS, media_common, Chronotherapy, business.industry, Irinotecan pharmacodynamics, medicine.disease, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Computer Science Applications, Irinotecan, Molecular circadian profiles, Toxicity, Cancer research, Cellular model, business, Drug metabolism, TP248.13-248.65, Research Article, medicine.drug, Biotechnology |
| الوصف: | Graphical abstract Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of treatment timing using a novel mathematical model of irinotecan cellular pharmacokinetics and –dynamics linked to a representation of the core clock and predict treatment toxicity in a colorectal cancer (CRC) cellular model. The mathematical model is fitted to three different scenarios: mouse liver, where the drug metabolism mainly occurs, and two human colorectal cancer cell lines representing an in vitro experimental system for human colorectal cancer progression. Our model successfully recapitulates quantitative circadian datasets of mRNA and protein expression together with timing-dependent irinotecan cytotoxicity data. The model also discriminates time-dependent toxicity between the different cells, suggesting that treatment can be optimized according to their cellular clock. Our results show that the time-dependent degradation of the protein mediating irinotecan activation, as well as an oscillation in the death rate may play an important role in the circadian variations of drug toxicity. In the future, this model can be used to support personalized treatment scheduling by predicting optimal drug timing based on the patient’s gene expression profile. |
| اللغة: | English |
| تدمد: | 2001-0370 |
| DOI: | 10.1016/j.csbj.2021.08.051⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::216f8d48230f132ae8ecd4b66ea596f4 http://www.sciencedirect.com/science/article/pii/S2001037021003822 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....216f8d48230f132ae8ecd4b66ea596f4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20010370 |
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| DOI: | 10.1016/j.csbj.2021.08.051⟩ |