Reovirus and other oncolytic viruses for the targeted treatment of cancer

In the last 50 years, there have been a number of anecdotal reports of viral infections causing transient cancer remissions in patients with advanced disease. However, during the last decade, these reports have been supplemented by data indicating the potential antitumor effect of a number of viruses. As a consequence, there has been increasing interest in the development of oncolytic viruses-viruses that selectively destroy cancer cells-as cancer therapeutics. They can be divided into two groups: natural tumor-selective wild-type viruses and genetically engineered tumor-selective viruses; both present advantages and disadvantages. The use of oncolytic viruses as anticancer agents still represents a major challenge and many obstacles need to be overcome: issues of systemic toxicity, tumor selectivity, immune response, and manufacture are added to the inconvenience of genetic manipulation. Reovirus is an inherently selective wild-type virus that seems to fulfill many of the above criteria for an oncolytic virus. Reovirus selectively replicates in Ras-activated cells and has been shown to possess antitumor activity both in vitro and in vivo. Since many tumors have an activated Ras pathway, the potential for using reovirus as an effective anticancer agent is substantial. Ongoing studies have demonstrated its safety when administered to cancer patients.