Oncolytic Viruses in the Treatment of Bladder Cancer
Oncolytic mechanism of reovirus. Similar to HSV in normal or untransformed cells, double-stranded reovirus RNA activates the double-stranded-RNA- (dsRNA-) dependent protein kinase (PKR), which causes eIF2α phosphorylation and inhibition of translation of the viral genes. In many cancer cells there is an activated epidermal growth factor receptor (EGFR) or mutation in downstream signaling cascades such as Ras. This dysregulated growth factor signaling means PKR is not phosphorylated thus allowing translation of viral genes and a productive lytic infection that results in cell lysis.