Quantitative imaging and dynamics of tumor therapy with viruses.

Cancer therapy remains challenging due to the myriad presentations of the disease and the vast genetic diversity of tumors that continuously evolve and often become resistant to therapy. Viruses can be engineered to specifically infect, replicate, and kill tumor cells (tumor virotherapy). Moreover, the viruses can be "armed" with therapeutic genes to enhance their oncolytic effect. Using viruses to treat cancer is exciting and novel and in principle can be used for a broad variety of tumors. However, the approach is distinctly different from other cancer therapies since success depends on establishment of an infection within the tumor and ongoing propagation of the oncolytic virus within the tumor itself. Therefore, the target itself amplifies the therapy. This introduces complex dynamics especially when the immune system is taken into consideration as well as the physical and other biological barriers to virus growth. Understanding these dynamics not only requires mathematical and computational models but also approaches for the noninvasive monitoring of the virus and tumor populations. In this perspective, we discuss strategies and current results to achieve this important goal of understanding these dynamics in pursuit of optimization of oncolytic virotherapy.