Combined therapy for treating solid tumors with chemotherapy and angiogenic inhibitors

1. Introduction. Cancer is one of the major causes of death in developed countries that continues to cause great hardship for humankind. The complex processes underlying its development continue to attract much attention from scientists across a variety of disciplines, and as such, research dedicated to understanding and combatting cancer is one of the most active areas in biomedicine. The National Cancer Institute, an affiliate of the National Institutes of Health, estimates that 1.8 million ABSTRACT Anti-angiogenesis therapy has been an emerging cancer treatment which may be further combined with chemotherapy to enhance overall survival of cancer patients. In this paper, we investigate a system of nonlinear ordinary differential equations describing a microenvironment consisting of host cells, tumor cells, immune cells and endothelial cells while incorporating treatment combination with chemotherapy and anti-angiogenesis therapy. We perform a dynamical systems analysis demonstrating that our model is able to capture the three phases of cancer immunoediting: elimination, equilibrium, and escape. In addition, we present transcritical bifurcations for relevant parameter values that correspond to the progression from the elimination phase to the equilibrium phase. A range of medically useful tumor doubling times were simulated to determine how combined therapy affects the tumor microenvironment over the course of a 250 day treatment. This analysis found two additional bifurcation parameters that move the system of equations from the equilibrium phase to the elimination phase. We determine that the most important aspect of an effective therapy is the activation of the anti-tumor immune response.