Oncolytic viruses for potential osteosarcoma therapy

Since the first anecdotal reports of dramatic tumor responses following a viral infection in early 1900s, the field of oncolytic virotherapy has evolved at a rapid pace finally making its way into clinical trials. A large number of both wild-type and genetically altered viruses with a preferential replication-competency for tumor cells have been studied in tissue cultures, animal models and in humans, with an ever increasing repertoire of new viruses being added to this pool. Although oncolytic viruses have caused dramatic antitumor responses in cell cultures and mouse models, their clinical effects in humans have been modest. Therefore, the current research is focused on understanding the mechanisms by which viruses kill tumor cells, the barriers to successful viral delivery and penetration into tumor cells, the role of the immune system in viral oncolysis and generating stronger target specifi c and replication competent viruses. Osteosarcoma is a challenging malignancy to identify novel targets for therapy due to its complex genetic make-up. Oncolytic virotherapy may be a promising approach as a novel therapeutic, not dependent on consistent expression of a single target. In this review we summarize the supportive evidence and rationale for use of viral oncolysis in osteosarcoma along with the specifi c challenges it may face.