Department of Mathematics, University of California Irvine, Irvine, California, USA.
Department of Medicine, UCSD School of Medicine, San Diego, California, USA.
Wiley Interdiscip Rev Syst Biol Med. 2020 Sep;12(5):e1487. doi: 10.1002/wsbm.1487. Epub 2020 Mar 12.
Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in hereditary forms of the disease. The mechanisms underlying this protective effect, however, are incompletely understood. The molecular events that lead to protection have been partly defined, but remain to be fully characterized. So far, however, approaches based on evolutionary dynamics have not been discussed much, but can potentially offer important insights. The aim of this review is to highlight this line of investigation and the results that have been obtained. A core observation in this respect is that aspirin has a direct negative impact on the growth dynamics of the cells, by influencing the kinetics of tumor cell division and death. We discuss the application of mathematical models to experimental data to quantify these parameter changes. We then describe further mathematical models that have been used to explore how these aspirin-mediated changes in kinetic parameters influence the probability of successful colony growth versus extinction, and how they affect the evolution of the tumor during aspirin administration. Finally, we discuss mathematical models that have been used to investigate the selective forces that can lead to the rise of mismatch-repair deficient cells in an inflammatory environment, and how this selection can be potentially altered through aspirin-mediated interventions. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Analytical Methods Analytical and Computational Methods > Computational Methods.
流行病学数据表明，长期低剂量阿司匹林治疗对散发性和遗传性结直肠癌的发生具有保护作用。然而，这种保护作用的机制尚不完全清楚。导致这种保护作用的分子事件部分已被定义，但仍有待全面描述。然而，到目前为止，基于进化动力学的方法还没有被广泛讨论，但它们可能提供重要的见解。本文旨在强调这一研究方向以及已经取得的研究成果。这方面的一个核心观察结果是，阿司匹林通过影响肿瘤细胞分裂和死亡的动力学，直接对细胞的生长动态产生负面影响。我们讨论了将数学模型应用于实验数据以量化这些参数变化的方法。然后，我们描述了进一步的数学模型，这些模型被用来探索阿司匹林介导的这些动力学参数变化如何影响成功集落生长与灭绝的概率，以及它们如何影响阿司匹林治疗期间肿瘤的进化。最后，我们讨论了用于研究在炎症环境中可能导致错配修复缺陷细胞出现的选择压力的数学模型，以及通过阿司匹林介导的干预如何改变这种选择。本文属于以下类别： 系统性质和过程的模型 > 机制模型 分析和计算方法 > 分析方法 分析和计算方法 > 计算方法
