Reovirus therapy in cancer: Has the orphan virus found a home?

There has been great interest in the development of oncolytic viruses - viruses that selectively destroy tumour cells - as cancer therapeutics. Reovirus holds great promise as an anticancer therapy, not just because it is a wild type virus that inherently displays selective tumour cytotoxicity in cancers with active Ras signalling pathways but also because it results only in relatively benign infections with few minor symptoms. As many tumours have an activated Ras pathway, the potential for utilizing reovirus as an effective anticancer agent is substantial. The several challenges that need to be overcome in the development of oncolytic viruses as anticancer agents, including issues of systemic toxicity, tumour selectivity and immune response, are addressed in this review. Clinical studies with the objective of developing Reolysin (human reovirus serotype 3 Dearing) as a human cancer therapeutic are currently underway. The first human Phase I study with intravenous Reolysin has now been completed and further studies, including Phase I and II clinical trials using Reolysin alone and in combination with radiation or chemotherapy, delivered via local or systemic intravenous administration, have commenced.