The Impact of Microenvironmental Heterogeneity on the Evolution of Drug Resistance in Cancer Cells.

ABSTRACT: Therapeutic resistance arises as a result of evolutionary processes driven by dynamic feedback between a heterogeneous cell population and environmental selective pressures. Previous studies have suggested that mutations conferring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small-cell lung cancer (NSCLC) cells lower the fitness of resistant cells relative to drug-sensitive cells in a drug-free environment. Here, we hypothesize that the local tumor microenvironment could influence the magnitude and directionality of the selective effect, both in the presence and absence of a drug. Using a combined experimental and computational approach, we developed a mathematical model of preexisting drug resistance describing multiple cellular compartmen

SUBMITTER: Mumenthaler SM 

PROVIDER: S-EPMC4504404 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature