Functional heterogeneity, tumor vascularization, and the nonlinear dynamics of metastatic cancer treated by oncolytic viral therapy

Oncolytic viral therapy (OVT) is an emerging cancer treatment where therapeutic viruses are injected into a patient. Models have been developed which describe the interactions of the virus, tumor and immune system through systems of nonlinear ordinary differential equations (ODEs). Some suggest that an initial phase of treatment with immunosuppressants could improve the efficacy of OVT by preventing the immune system from attacking the oncolytic viruses before they can infect many tumor cells. However, all such models have focused on a single, localized tumor. Here, we model a primary tumor and its continuous metastatic seeding of a secondary organ under simplifying assumptions about tumor vascularization. Bifurcation analysis and simulations reveal regions in parameter space for which immune modulation encourages distant metastasis, leading to the dangerous scenario where the elimination of a primary tumor creates the false impression of a good prognosis. We also suggest that vascular disrupting agents may be useful for treating small tumors while they may promote OVT resistance in larger tumors.