Cancer does not always develop to become a clinically manifest disease. Most of the population actually carries small occult tumors that remain asymptomatic and undetectable. Here, we propose a theoretical study of this phenomenon by defining and simulating a novel mathematical model able to describe the development of a population of tumors at the organism scale. After demonstrating the model can explain experimental data on metastatic development, we go on to test the hypothesis of global dormancy resulting from inhibitory signaling interactions among the tumors. These interactions are targeted against the tumor's vascular support development (angiogenesis), known to be essential for tumor growth, by means of inhibitory molecules released in the circulation. By quantifying their consequences on the establishment of metastases and maintenance of the dormant state, our model shows for the first time how a previously unrecognized phenomenon - systemic inhibition of angiogenesis (SIA) - regulates tumor development. We show SIA alone is not sufficient for global dormancy but can suppress the growth of the total metastatic burden, even to the point of producing an equilibrium state with low and stable total cancerous mass.
Sebastien BenzekryAlberto GandolfiPhilip Hahnfeldt