The Impact of Cell Density and Mutations in a Model of Multidrug Resistance in Solid Tumors

被引：32

作者：

Greene, James ^{[1
,2
]}

Lavi, Orit ^{[3
]}

Gottesman, Michael M. ^{[3
]}

Levy, Doron ^{[1
,2
]}

机构：

[1] Univ Maryland, Dept Math, College Pk, MD 20742 USA

[2] Univ Maryland, Ctr Sci Computat & Math Modeling CSCAMM, College Pk, MD 20742 USA

[3] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA

来源：

BULLETIN OF MATHEMATICAL BIOLOGY | 2014年 / 76卷 / 03期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Multidrug resistance; Chemotherapy; Mutation; Heterogeneity; Integro-differential equations; DRUG-RESISTANCE; MATHEMATICAL-MODEL; INTRATUMORAL HETEROGENEITY; GENE AMPLIFICATION; DYNAMICS; APOPTOSIS; CHEMOTHERAPY; SENSITIVITY; ADAPTATION; SELECTION;

D O I：

10.1007/s11538-014-9936-8

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In this paper we develop a mathematical framework for describing multidrug resistance in cancer. To reflect the complexity of the underlying interplay between cancer cells and the therapeutic agent, we assume that the resistance level is a continuous parameter. Our model is written as a system of integro-differential equations that are parameterized by the resistance level. This model incorporates the cell density and mutation dependence. Analysis and simulations of the model demonstrate how the dynamics evolves to a selection of one or more traits corresponding to different levels of resistance. The emerging limit distribution with nonzero variance is the desirable modeling outcome as it represents tumor heterogeneity.

引用

页码：627 / 653

页数：27

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