Combinatorial and personalized oncolytic virotherapy in the battle against glioblastoma

Oncolytic virotherapy (OV) is a promising strategy for difficult-to-treat cancers. Glioblastoma (GBM) is such an aggressive type of brain cancer with poor survival due to tumor recurrence in all patients. Current treatment options are very limited and ineffective. Consequently, novel intervention strategies that can be given after recurrence or in combination with the standard-of-care at primary diagnosis are highly needed. However, no OV is associated with encouraging clinical results yet. One of the reasons for these suboptimal clinical results is the high inter- and intratumoral heterogeneity, by which outcome differs among patients and time of diagnosis. In addition, there is only limited knowledge on virological aspects of OV. For example, the effect of cellular proviral host factors on OV response has not been studied, while this information is essential for successful translation of OV to the clinic. Therefore, I will study a wide variety of viruses in an extended set of patient-derived GBM cell lines, and I will identify proviral host factors essential for viral replication and virus-induced cytopathogenic effect in these cell lines. These factors may serve as predictive markers for successful OV, which will contribute to establishment of personalized treatment in GBM.