The Tumor Invasion Paradox in Cancer Stem Cell-Driven Solid Tumors

Cancer stem cells (CSCs) are key in understanding tumor growth and tumor progression. A counterintuitive effect of CSCs is the so-called tumor growth paradox: the effect where a tumor with a higher death rate may grow larger than a tumor with a lower death rate. Here we extend the modeling of the tumor growth paradox by including spatial structure and considering cancer invasion. Using agent-based modeling and a corresponding partial differential equation model, we demonstrate and prove mathematically a tumor invasion paradox: a larger cell death rate can lead to a faster invasion speed. We test this result on a generic hypothetical cancer with typical growth rates and typical treatment sensitivities. We find that the tumor invasion paradox may play a role for continuous and intermittent treatments, while it does not seem to be essential in fractionated treatments. It should be noted that no attempt was made to fit the model to a specific cancer, thus, our results are generic and theoretical.