Institute for Systems Medicine, Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg, 20457, Germany.
Institute for Theoretical Biology (ITB), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 10117, Germany.
NPJ Syst Biol Appl. 2023 Jun 23;9(1):27. doi: 10.1038/s41540-023-00287-4.
Increasing evidence points to a role of the circadian clock in the regulation of cancer hallmarks with a strong impact on the understanding and treatment of this disease. Anti-cancer treatment can be personalized considering treatment timing. Here we present a new mathematical model based on data from three colorectal cancer cell lines and core-clock knock-outs, which couples the circadian and drug metabolism network, and that allows to determine toxicity profiles for a given drug and cell type. Moreover, this model integrates external Zeitgebers and thus may be used to fine-tune toxicity by using external factors, such as light, and therefore, to a certain extent, help fitting the endogenous rhythms of the patients to a defined clinic routine facilitating the implementation of time-dependent treatment in clinical practice.
越来越多的证据表明，生物钟在调节癌症特征方面发挥着重要作用，这对理解和治疗这种疾病有重大影响。可以考虑治疗时间来实现癌症治疗的个体化。在这里，我们提出了一个新的数学模型，该模型基于来自三种结直肠癌细胞系和核心时钟敲除体的数据，它将生物钟和药物代谢网络耦合起来，能够为特定药物和细胞类型确定毒性特征。此外，该模型还整合了外部时间信号，因此可以通过使用外部因素（如光照）来微调毒性，从而在一定程度上帮助患者的内源性节律与特定的临床常规相适应，促进时间依赖性治疗在临床实践中的实施。
