Optimizing antiangiogenic therapy for tumor minimization

In this paper, optimization of antiangiogenic therapy for tumor management is considered as a nonlinear control problem. A new technique is developed to optimize antiangiogenic therapy which minimizes the volume of a tumor and prevents it from growing using an optimum drug dose. To this end, an optimum desired trajectory is designed to minimize a performance index. Two controllers are then presented that drive the tumor volume to its optimum value. The first controller is proven to yield exponential results given exact model knowledge. The second controller is developed under the assumption of parameteric uncertainties in the system model. A least-squares estimation strategy based on a prediction error formulation and a Lyapunov-type stability analysis is developed to estimate the unknown parameters of the performance index. An adaptive controller is then designed to track the desired optimum trajectory. The proposed tumor minimization scheme is shown to minimize the tumor volume with an optimum drug dose despite the lack of knowledge of system parameters.