Multiscale modeling of tumor response to vascular endothelial growth factor (VEGF) inhibitor.

Abstract

Vascular endothelial growth factor (VEGF) has been known as a key mediator of angiogenesis in cancer. Bevacizumab is anti-VEGF monoclonal antibody that has been approved by the FDA as a first-line treatment in many types of cancer. In this paper, we extend a previously validated multiscale tumor model to comprehensively include the multiple roles of VEGF during the course of angiogenesis and its binding mechanism with bevacizumab. We use the model to simulate tumor system response under various bevacizumab concentrations, both in stand-alone treatment and in combination with chemotherapy. Our simulation indicates that periodic administration of bevacizumab with lower concentration can achieve greater efficacy than a single treatment with higher concentration. The simulation of the combined therapy also shows that the continuous administration of bevacizumab during the maintenance phase can lead to antitumor activity which further suppresses its growth. Agreement with experimental results indicates the potential of the model in predicting the efficacy of anti-VEGF therapies and could therefore contribute to developing prospective clinical trials.