title: The impact of cell density and mutations in a model of multidrug resistance in solid tumors.
abstract: 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.
authors.affiliation: Department of Mathematics and Center for Scientific Computation and Mathematical Modeling (CSCAMM), University of Maryland, College Park, MD, 20742, USA.
authors.forename: James
authors.initials: J
authors.lastname: Greene
authors.forename: Orit
authors.initials: O
authors.lastname: Lavi
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottesman
authors.forename: Doron
authors.initials: D
authors.lastname: Levy
mesh_terms: D002452:Cell Count; D003198:Computer Simulation; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D055641:Mathematical Concepts; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology