Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses.

Increased sensitivity of cancer cells to viruses is a prerequisite for the success of oncolytic virotherapy. One of the major causes of such a phenotype is the disruption of innate antiviral defenses associated with dysfunction of type 1 interferons (IFNs) that permits unlimited replication of viruses in cancer cells. Defects in IFN pathways help cancer progression by providing additional advantages to tumor cells. However, while these defects promote the survival and accelerated proliferation of malignant cells, they facilitate viral replication and thus enhance the efficiency of viral oncolysis. This review describes a broad spectrum of defects in genes that participate in IFN induction and IFN response pathways. Expression levels and/or functional activities of these genes are frequently low or absent in cancer cells, making them sensitive to virus infection. Therefore, certain specific defects in IFN signaling cascades might serve as potential biomarkers to help in identifying individual cancer patients who are likely to benefit from oncolytic virotherapy.