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bioRxiv · 10.1101/2021.12.01.470781

Mathematical characterization of population dynamics in breast cancer cells treated with doxorubicin

Yang, E. Y.·Howard, G. R.·Brock, A.·Yankeelov, T. E.·Lorenzo, G.
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Abstract

The development of chemoresistance remains a significant cause of treatment failure in breast cancer. We posit that a mathematical understanding of chemoresistance could assist in developing successful treatment strategies. Towards that end, we have developed a model that describes the effects of the standard chemotherapeutic drug doxorubicin on the MCF-7 breast cancer cell line. We assume that the tumor is composed of two subpopulations: drug-resistant cells, which continue proliferating after treatment, and drug-sensitive cells, which gradually transition from proliferating to treatment-induced death. The model is fit to experimental data including variations in drug concentration, inter-treatment interval, and number of doses. Our model recapitulates tumor growth dynamics in all these scenarios (as quantified by the concordance correlation coefficient, CCC > 0.95). In particular, superior tumor control is observed with higher doxorubicin concentrations, shorter inter-treatment intervals, and a higher number of doses (p < 0.05). Longer inter-treatment intervals require adapting the model parameterization after each doxorubicin dose, suggesting the promotion of chemoresistance. Additionally, we propose promising empirical formulas to describe the variation of model parameters as functions of doxorubicin concentration (CCC > 0.78). Thus, we conclude that our mathematical model could deepen our understanding of the effects of doxorubicin and could be used to explore practical drug regimens achieving optimal tumor control.

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Yang, E. Y., Howard, G. R., Brock, A., Yankeelov, T. E., Lorenzo, G.. 2021-12-03. Mathematical characterization of population dynamics in breast cancer cells treated with doxorubicin. https://doi.org/10.1101/2021.12.01.470781

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