Antiangiogenic Therapy Efficacy Can Be Tumor Size Dependent,as Mathematical Modeling Suggests

Abstract

Antiangiogenic therapy (AAT) is an indirect oncological modality which is aimed at disruption of cancer cells nutrient supply. Invasive tumors have been shown to possess inherent resistant to this treatment, while compactly growing benign tumors react to it by shrinkage. It is generally accepted that AAT by itself is not curative. This study presents a mathematical model of non-invasive tumor growth with physiologically justified account of alteration of microvasculature and biomechanical aspects during tumor growth and AAT. In untreated setting the model reproduces tumor growth with saturation, where the maximum tumor volume depends on the level of angiogenesis. The outcomes of simulations of AAT depend on the tumor size at the moment of treatment initiation. If it is close to the stable size of avascular tumor grown in absence of angiogenesis, then the tumor is rapidly stabilized by AAT. Treatment of large tumors is accompanied by displacement of normal tissue due to the tumor shrinkage. During it, microvasculature undergoes distortion which degree depends on the displacement distance. As it affects tumor nutrient supply, the stable size of a tumor that undergoes AAT negatively correlates with its size at the beginning of treatment. For sufficiently large initial tumors, the long-term survival of tumor cells is compromised by competition with normal cells for severely limited inflow of nutrients, which makes AAT effectively curative.