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Singular controls and chattering arcs in optimal control problems arising in biomedicine

Ledzewicz U., Schattler H.

Control and Cybernetics

2009

Vol. 38, no 4B

1501-1523

We consider an optimal control problem of the Mayer-type for a single-input, control affine, nonlinear system in small dimension. In this paper, we analyze effects that a modeling extension has on the optimality of singular controls when the control is replaced with the output of a first-order, time-invariant linear system driven by a new control. This analysis is motivated by an optimal control problem for a novel cancer treatment method, tumor anti-angiogenesis, when such a linear differential equation, which represents the pharmacokinetics of the therapeutic agent, is added to the model. We show that formulas that define a singular control of order 1 and its associated singular arc carry over verbatim under this model extension, albeit with a different interpretation. But the intrinsic order of the singular control increases to 2. As a, consequence, optimal concatenation sequences with the singular control change and the possibility of optimal chattering arcs arises.

Direct and indirect control of cancer populations

Świerniak A.

Bulletin of the Polish Academy of Sciences. Technical Sciences

2008

Vol. 56, nr 4

367-378

This paper presents a brief survey of our research in which we have used control theoretic methods in modelling and control of cancer populations. We focus our attention on two classes of problems: optimization of anticancer chemotherapy taking into account both phase specificity and drug resistance, and modelling, and optimization of antiangiogenic therapy. In the case of chemotherapy the control action is directly aimed against the cancer cells while in the case of antiangiogenic therapy it is directed against normal cells building blood vessels and only indirectly it controls cancer growth. We discuss models (both finite and infinite dimensional) which are used to find conditions for tumour eradication and to optimize chemotherapy protocols treating cell cycle as an object of control. In the case of antiangiogenic therapy we follow the line of reasoning presented by Hahnfeldt et al. who proposed to use classical models of self-limiting tumour growth with variable carrying capacity defined by the dynamics of the vascular network induced by the tumour in the process of angiogenesis. In this case antiangiogenic protocols are understood as control strategies and their optimization leads to new recommendations for anticancer therapy.

Qualitative analysis of controlled drug resistance model - inverse Laplace and and semigroup approach

Świerniak A., Polański A., Kimmel M., Bobrowski A., Śmieja J.

Control and Cybernetics

1999

Vol. 28, no 1

61-73

In this paper we study some properties of infinite models of the controlled evolution of drug resistance. We combine asymptotic techniques used in previous studies of similar models with methods of control theory and of semigroup theory. It enables us to find conditions for stability of the model both when the sensitive population is annihilated and when there exists a permanent influx from the sensivite compartment into drug resistant one. The conditions are expressed in terms of relationships between amplification and deamplification ratios as well as average life times of cells and intensity of anticancer drug action.