Model-Based Simulation and Comparison of Open-Loop and Closed-Loop Combined Therapies for Tumor Treatment

Abstract

Targeted molecular therapies opened new ways and increased the efficiency of cancer therapies. Antiangiogenic therapy focuses against the growth of tumor by blocking the blood vessel formation of it. Its control engineering perspective has been presented several times, but its key point represents modeling the tumor growth. The purpose of our research is to go beyond the already published minimalistic approach and set up a bi-compartmental (vasculature-dependent tumor growth and angiogenesis) model. The aim of the current paper is to extend our recently published dynamical bicompartmetal model to include the effect of not only for antiangiogenic, but also cytotoxic drugs as well as input. We compare the effect of the two different inputs on the model dynamics in the context of final tumor volume, which can be used as a measure of therapy effectiveness. According to the model prediction, the combination of drugs is more efficient compared to either monotherapy. Furthermore, we compare an optimized open-loop protocol with a very simple intuitive feedback therapy solution.

Dynamic Modeling of the Angiogenic Switch and Its Inhibition by Bevacizumab

“…Furthermore, the model in [35] was fitted only for measurement data originating from protocol 1, while the proposed model has been validated against both protocol 1 and protocol 2. Similar to the model described in [35], the model proposed in the current article also allows for the analysis of combined therapies, as done in the article in [61].…”

“…Models with predictive power regarding the efficiency of combined therapies and model-based optimization of such treatments are not prevalent in literature. Some initial results on the optimization of combined therapies are described in [61], using the model of [35].…”