Control Theory and Cancer Chemotherapy: How They Interact.

Control theory arises in most modern real-life applications, not least in biological and medical applications. In particular, in biological and medical contexts, the role of control theory began to take shape in the early 1980s when the first works appeared on the application of control theory in models of pharmacokinetics and pharmacodynamics for antitumor therapies. Forty years after those first works, the theory of control continues to be considered a mathematical analysis tool of extreme importance and usefulness, but the challenges it must overcome in order to manage the complexity of biological processes are in fact not yet overcome. In this article, we introduce the reader to the basic ideas of control theory, its aims and its mathematical formalization, and we review its use in cell phase-specific models for cancer chemotherapy. We discuss strengths and limitations of the control theory approach to the analysis pharmacokinetics and pharmacodynamics models, and we will see that most of them are strongly related to data availability and mathematical form of the model. We propose some future research directions that could prove useful in overcoming the these limitations and we indicate the crucial steps preliminary to a useful and informative application of control theory to cancer chemotherapy modeling.