Closed-loop nonlinear smooth robust control of anti-angiogenic tumor therapy

This paper presents a smooth robust controller for anti-angiogenic treatment of a tumor growth. The proposed control algorithm directly aims to drive the carrying capacity of the vascular support network to a desired trajectory that reduces overall tumor volume. For this aim, we present a closed-loop smooth robust controller that ensures the asymptotic tracking of a time-varying carrying capacity profile, despite the model uncertainties. A Lyapunov-based analysis approach is used to determine stability and performance results. Numerical simulation results are presented to demonstrate the performance and feasibility of the proposed approach. Simulation studies also examine some practical issues regarding the clinical application of the proposed dosing algorithm. Finally, the paper provides some basics for real-time implementation of the overall system.