*6.3. Combination of VSV with FDA-Approved Chemotherapeutic Drugs*

VSV is inherently oncoselective due to its high sensitivity to type 1 IFN response, as research indicates that most cancer cells are defective in this type of antiviral signaling, and VSV-∆M51 is more sensitive than the WT virus, which is better able to inhibit these responses. G2/M arrest stimulates viral replication by inhibiting antiviral responses. Paclitaxel treatment stimulated the replication of VSV-∆M51 and Sendai virus (another cytoplasmic NNS RNA virus that is also sensitive to type 1 IFN response) in multiple PDAC cell lines via inhibition of antiviral gene expression in treated cells [61]. In cells with functional type I IFN signaling, G2/M arrest inhibited the expression levels of type I and III IFNs, as well as inhibiting the upregulation of ISGs in response to the same amounts of exogenously added type I IFN [61]. A similar effect was also shown for colchicine [193].
