Since the 1960's oncolytic viruses (OVs) have been a target of research as a therapeutic modality for cancer. The mechanism of these viruses involves both direct tumor cell lysis and the induction of immunogenic cell death (ICD). Clinical trials have explored a wide variety of viruses including naturally occurring viruses and genetically engineered viruses. Indications have spanned the gamut from hepatocellular carcinoma to soft tissue sarcoma to glioblastoma multiforme to multiple myeloma. In the past year, the U.S. Food and Drug Administration announced the first FDA-approved oncolytic virus therapy, for the treatment of melanoma lesions in the skin and lymph nodes. Oncolytic viruses have been used as single agent therapy or in combination with conventional cancer therapies. Current challenges including both scientific and regulatory do not diminish the significant potential for the future of this modality. Questions about the advantages of one virus over the other, the synergistic potential of multiple viruses used in combination, dosage, and optimal route of administration remain unresolved and demand further research. Furthermore, the possibility that a particular oncolytic virus might be more suitable for a specific cancer type than other oncolytic viruses depending on the mechanism of the virus and the nature of the cancer raises additional research challenges. The precise role of adjuvant therapies such as dendritic cells in combination with oncolytic viruses is yet another unresolved area in this innovative field.

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