Adaptive dynamics of unstable cancer populations: The canonical equation
Adaptive dynamics of unstable cancer populations: The canonical equation
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DOI：
10.1111/eva.12625
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发表时间：
2018-09-01
影响因子：
4.1
通讯作者：
Sole, Ricard
中科院分区：
文献类型：
--
作者：
Aguade-Gorgorio, Guim;Sole, Ricard
在肿瘤发展的大多数情况下，遗传不稳定性在允许癌细胞群体对选择障碍（如物理限制或免疫反应）做出反应并迅速适应不断变化的环境中发挥作用。对不稳定性进行建模是一项重要的任务，因为根据定义，不断演变的不稳定性会导致底层景观的变化。在这篇文章中，我们探索数学上的一个简单版本的不稳定的肿瘤进展使用的形式主义的自适应动力学（AD），其中选择和突变明确耦合。使用一组基本的健身景观，所谓的典型方程的遗传不稳定性的进化的最小的情况下，与一个人口的不稳定的细胞。我们得到明确的表达突变概率的演变，并进一步的实验研究和潜在的诱变治疗模型的影响进行了讨论。
In most instances of tumour development, genetic instability plays a role in allowing cancer cell populations to respond to selection barriers, such as physical constraints or immune responses, and rapidly adapt to an always changing environment. Modelling instability is a nontrivial task, since by definition evolving instability leads to changes in the underlying landscape. In this article, we explore mathematically a simple version of unstable tumour progression using the formalism of adaptive dynamics (AD) where selection and mutation are explicitly coupled. Using a set of basic fitness landscapes, the so-called canonical equation for the evolution of genetic instability on a minimal scenario associated with a population of unstable cells is derived. We obtain explicit expressions for the evolution of mutation probabilities, and the implications of the model on further experimental studies and potential mutagenic therapies are discussed.