Mathematical Details on a Cancer Resistance Model.

One of the most important factors limiting the success of chemotherapy in cancer treatment is the phenomenon of drug resistance. We have recently introduced a framework for quantifying the effects of induced and non-induced resistance to cancer chemotherapy (Greene et al., 2018a, 2019). In this work, we expound on the details relating to an optimal control problem outlined in Greene et al. (2018a). The control structure is precisely characterized as a concatenation of bang-bang and path-constrained arcs via the Pontryagin Maximum Principle and differential Lie algebraic techniques. A structural identifiability analysis is also presented, demonstrating that patient-specific parameters may be measured and thus utilized in the design of optimal therapies prior to the commencement of therapy. For completeness, a detailed analysis of existence results is also included.