biostudies-literatureLavi OIntramural NIH HHSNCI NIH HHS7168-75https://www.ebi.ac.uk/biostudies/studies/S-EPMC4782773biostudies-literatureUnknown73(24)Recent data have demonstrated that cancer drug resistance reflects complex biologic factors, including tumor heterogeneity, varying growth, differentiation, apoptosis pathways, and cell density. As a result, there is a need to find new ways to incorporate these complexities in the mathematical modeling of multidrug resistance. Here, we derive a novel structured population model that describes the behavior of cancer cells under selection with cytotoxic drugs. Our model is designed to estimate intratumoral heterogeneity as a function of the resistance level and time. This updated model of the multidrug resistance problem integrates both genetic and epigenetic changes, density dependence, and intratumoral heterogeneity. Our results suggest that treatment acts as a selection process, whereas gCancer researchThe role of cell density and intratumoral heterogeneity in multidrug resistance.PMC4782773R01 CA130817R01CA130817Z01 BC010830-01Levy DGottesman MMLavi OGreene JMfalseThe role of cell density and intratumoral heterogeneity in multidrug resistance.Recent data have demonstrated that cancer drug resistance reflects complex biologic factors, including tumor heterogeneity, varying growth, differentiation, apoptosis pathways, and cell density. As a result, there is a need to find new ways to incorporate these complexities in the mathematical modeling of multidrug resistance. Here, we derive a novel structured population model that describes the behavior of cancer cells under selection with cytotoxic drugs. Our model is designed to estimate intratumoral heterogeneity as a function of the resistance level and time. This updated model of the multidrug resistance problem integrates both genetic and epigenetic changes, density dependence, and intratumoral heterogeneity. Our results suggest that treatment acts as a selection process, whereas g2013-01-01T00:00:00Z2013 Dec2025-04-05T10:27:25.904Z2019-03-27T02:10:40ZS-EPMC47827732416338010.1158/0008-5472.CAN-13-176810.1158/0008-5472.can-13-1768