Tumor development under angiogenic signaling: A dynamical theory of tumor growth, treatment response, and postvascular dormancy

The effects of the angiogenic inhibitors endostatin, angiostatin, and TNP-4 70 on tumor growth dynamics are experimentally and theoretically investigat ed. On the basis of the data, we pose a quantitative theory for tumor growt h under angiogenic stimulator/inhibitor control that is both explanatory an d clinically implementable. Our analysis offers a ranking of the relative e ffectiveness of these inhibitors. Additionally, it reveals the existence of an ultimate limitation to tumor size under angiogenic control, where oppos ing angiogenic stimuli come into dynamic balance, which can be modulated by antiangiogenic therapy. The competitive influences of angiogenically drive n growth and inhibition underlying this framework may have ramifications fo r tissue size regulation in general.