Design of robust control strategy in drug and virus scheduling in nonlinear process of chemovirotherapy

Abstract

Since the injection of the oncolytic viruses in the virotherapy process reduces the toxicity and drug resistance inherent in the chemotherapy; chemovirotherapy as a novel combination therapy has become an efficient cancer treatment. The primary purpose of this paper is to design a robust optimal control strategy for the chemovirotherapy through which the tumor density decreases to its stable condition with limited drug and virus delivery. This desired treatment should be responsive in the presence of input disturbances and parametric uncertainties. In this regard, an ODE (Ordinary Differential Equation) mathematical model of the chemovirotherapy process presenting the connection between the avascular tumor cells, immune cells, and treatment materials is utilized. H-infinity and DK iteration controllers are designed and implemented to the uncertain model, through the continuous and discrete procedures. By comparing the closed-loop simulations, discrete injection is found to be more effective (while is also more realistic in practice). The characteristics of an optimal treatment including the treatment frequency, drug and virus dosage, and suggested start time will be determined as the final results of this research.