caa a22 4500 606166122 CHVBK 20210128100656.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s10440-014-9952-6 doi (NATIONALLICENCE)springer-10.1007/s10440-014-9952-6 A 3-Compartment Model for Chemotherapy of Heterogeneous Tumor Populations [Elektronische Daten] [Urszula Ledzewicz, Kenneth Bratton, Heinz Schättler] We consider a mathematical model for cancer chemotherapy with a single agent that distinguishes three levels of sensitivities calling the subpopulations ‘sensitive', ‘partially sensitive' and ‘resistant'. We analyze the dynamic properties of the system under what could be considered metronomic (continuous, low-dose, constant) chemotherapy and, more generally, also consider the optimal control problem of minimizing the tumor burden over a prescribed therapy interval. Interestingly, when several levels of chemotherapeutic sensitivities are taken into account in the model, lower time-varying dose rates as they are given by singular controls become a treatment option. This is only the case once a significant residuum of resistant cells has been created in a simpler 2-compartment model that only considers sensitive and resistant cells. For heterogeneous tumor populations, a more modulated approach that varies the dose rates of the drugs may be more beneficial than the classical maximum tolerated dose approach pursued in medical practice. Springer Science+Business Media Dordrecht, 2014 Optimal control nationallicence Singular control nationallicence Metronomic chemotherapy nationallicence Ledzewicz Urszula Dept. of Mathematics and Statistics, Southern Illinois University Edwardsville, 62026-1653, Edwardsville, IL, USA aut Bratton Kenneth Dept. of Mathematics and Statistics, Southern Illinois University Edwardsville, 62026-1653, Edwardsville, IL, USA aut Schättler Heinz Dept. of Electrical and Systems Engineering, Washington University, 63130-4899, St. Louis, MO, USA aut Acta Applicandae Mathematicae Springer Netherlands 135/1(2015-02-01), 191-207 0167-8019 135:1<191 2015 135 10440 https://doi.org/10.1007/s10440-014-9952-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10440-014-9952-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ledzewicz Urszula Dept. of Mathematics and Statistics, Southern Illinois University Edwardsville, 62026-1653, Edwardsville, IL, USA aut NATIONALLICENCE 700 1- Bratton Kenneth Dept. of Mathematics and Statistics, Southern Illinois University Edwardsville, 62026-1653, Edwardsville, IL, USA aut NATIONALLICENCE 700 1- Schättler Heinz Dept. of Electrical and Systems Engineering, Washington University, 63130-4899, St. Louis, MO, USA aut NATIONALLICENCE 773 0- Acta Applicandae Mathematicae Springer Netherlands 135/1(2015-02-01), 191-207 0167-8019 135:1<191 2015 135 10440