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首页> 外文期刊>ESAIM. Mathematical modelling and numerical analysis >EVOLUTION OF CANCER CELL POPULATIONS UNDER CYTOTOXIC THERAPY AND TREATMENT OPTIMISATION: INSIGHT FROM A PHENOTYPE-STRUCTURED MODEL
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EVOLUTION OF CANCER CELL POPULATIONS UNDER CYTOTOXIC THERAPY AND TREATMENT OPTIMISATION: INSIGHT FROM A PHENOTYPE-STRUCTURED MODEL

机译：细胞毒性治疗与治疗优化下癌细胞群的演变：从表型结构模型见解

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摘要

We consider a phenotype-structured model of evolutionary dynamics in a population of cancer cells exposed to the action of a cytotoxic drug. The model consists of a nonlocal parabolic equation governing the evolution of the cell population density function. We develop a novel method for constructing exact solutions to the model equation, which allows for a systematic investigation of the way in which the size and the phenotypic composition of the cell population change in response to variations of the drug dose and other evolutionary parameters. Moreover, we address numerical optimal control for a calibrated version of the model based on biological data from the existing literature, in order to identify the drug delivery schedule that makes it possible to minimise either the population size at the end of the treatment or the average population size during the course of treatment. The results obtained challenge the notion that traditional high-dose therapy represents a "one-fits-all solution" in anticancer therapy by showing that the continuous administration of a relatively low dose of the cytotoxic drug performs more closely to i.e. the optimal dosing regimen to minimise the average size of the cancer cell population during the course of treatment.
机译：我们考虑一种暴露于细胞毒性药物作用的癌细胞群中进化动态的表型结构化模型。该模型由有关细胞群密度函数的演变的非本体抛物线方程组成。我们开发了一种用于构建模型方程的精确解决方案的新方法，其允许对细胞群体的尺寸和表型组成的响应药剂量和其他进化参数的变化来改善尺寸和表型组成的系统。此外，我们基于现有文献的生物数据解决了模型的校准版本的数值最佳控制，以识别药物递送时间表，使得可以最大限度地减少治疗结束或平均值的人口大小人口规模在治疗过程中。结果获得了传统高剂量治疗的观念，通过表明，通过表明相对低剂量的细胞毒性药物更接近即最佳给药方案，通过表现出相对低剂量的细胞毒性药物的连续给药在治疗过程中最小化癌细胞群的平均大小。

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