Optimal control of a mathematical model for cancer chemotherapy under tumor heterogeneity

Shuo  Wang; Heinz Schättler

doi:10.3934/mbe.2016040

Article Contents

2016, Volume 13, Issue 6: 1223-1240. Doi: 10.3934/mbe.2016040

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Optimal control of a mathematical model for cancer chemotherapy under tumor heterogeneity

Shuo Wang^1, and
Heinz Schättler^2,

1.
Dept. of Electrical and Systems Engineering, Washington University, St. Louis, Mo, 63130
2.
Dept. of Electrical and Systems Engineering, Washington University, St. Louis, Mo 63130

Received: December 2015

Revised: February 2016

Published online: August 2016

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Abstract

We consider cancer chemotherapy as an optimal control problem with the aim to minimize a combination of the tumor volume and side effects over an a priori specified therapy horizon when the tumor consists of a heterogeneous agglomeration of many subpopulations. The mathematical model, which accounts for different growth and apoptosis rates in the presence of cell densities, is a finite-dimensional approximation of a model originally formulated by Lorz et al. [18,19] and Greene et al. [10,11] with a continuum of possible traits. In spite of an arbitrarily high dimension, for this problem singular controls (which correspond to time-varying administration schedules at less than maximum doses) can be computed explicitly in feedback form. Interestingly, these controls have the property to keep the entire tumor population constant. Numerical computations and simulations that explore the optimality of bang-bang and singular controls are given. These point to the optimality of protocols that combine a full dose therapy segment with a period of lower dose drug administration.

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Mathematics Subject Classification: Primary: 49K15, 92B05; Secondary: 93C95.

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