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. 2016 Nov 7;6:36198. doi: 10.1038/srep36198

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Copyright © 2016, The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Latin hypercube sampling was performed on the following parameters: overall growth rate (k_s), overall kill rate (α_s), growth rate (k₁) and kill rate (α₁) of subpopulation 1, and the initial fraction of each subpopulation ( and ). See Supplementary Table S1 for the parameter range used. Provided with the constraint of equal tumor burden and tumor reduction following first round of treatment, we derived the corresponding growth rate (k₂) and kill rate (α₂) of subpopulation 2. For each given parameter set, we ran the ODE simulations and derived therapeutic metrics (tumor size, percent tumor reduction, and rate of change in tumor sensitivity). This was visualized on a two-dimensional heatmap of differential growth (k₂/k₁) versus differential killing.

Inline graphic — Latin hypercube sampling was performed on the following parameters: overall growth rate (k_s), overall kill rate (α_s), growth rate (k₁) and kill rate (α₁) of subpopulation 1, and the initial fraction of each subpopulation ( and ). See Supplementary Table S1 for the parameter range used. Provided with the constraint of equal tumor burden and tumor reduction following first round of treatment, we derived the corresponding growth rate (k₂) and kill rate (α₂) of subpopulation 2. For each given parameter set, we ran the ODE simulations and derived therapeutic metrics (tumor size, percent tumor reduction, and rate of change in tumor sensitivity). This was visualized on a two-dimensional heatmap of differential growth (k₂/k₁) versus differential killing.