阿司匹林与癌症的化学预防:数学和进化动力学视角。

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2020-09-01 Epub Date: 2020-03-12 DOI:10.1002/wsbm.1487
Natalia L Komarova, C Richard Boland, Ajay Goel, Dominik Wodarz
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引用次数: 0

摘要

流行病学数据表明,长期服用低剂量阿司匹林对散发性和遗传性结直肠癌的发生具有保护作用。然而,人们对这种保护作用的机制尚不完全清楚。导致保护作用的分子事件已经部分确定,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得到很多讨论,但有可能提供重要的见解。本综述旨在强调这一研究方向和已取得的成果。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,对细胞的生长动力学产生了直接的负面影响。我们讨论了数学模型在实验数据中的应用,以量化这些参数变化。然后,我们将进一步介绍一些数学模型,这些模型被用于探索阿司匹林介导的动力学参数变化如何影响菌落成功生长与消亡的概率,以及它们如何影响阿司匹林用药期间肿瘤的演变。最后,我们讨论了用于研究在炎症环境中导致错配修复缺陷细胞崛起的选择性力量的数学模型,以及如何通过阿司匹林介导的干预措施来改变这种选择。本文归类于系统属性和过程模型 > 机理模型 分析和计算方法 > 分析方法 分析和计算方法 > 计算方法。
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Aspirin and the chemoprevention of cancers: A mathematical and evolutionary dynamics perspective.

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.

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来源期刊
CiteScore
18.40
自引率
0.00%
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0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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