Viral oncolytic therapy is under intense investigation as a novel anticancer strategy. Both alone and in combination with other conventional treatment modalities, viral oncolytics exploit the natural cytotoxicity of viruses to directly kill tumor cells. Results from preclinical studies demonstrating the intricate interaction between oncolytic viruses, the targeted tumors and their hosts, has resulted in new strategies being developed to overcome the challenges of maximizing oncolytic viral efficacy while ensuring safety. Advances in genetic engineering and the understanding of tumor biology targeting every step of the inherent host-virus interaction have allowed the design of novel viruses that selectively target, preferentially replicate in, and destroy cancer cells. A number of these oncolytic viruses have the potential to become powerful anticancer agents, especially against advanced solid tumors. The theory behind their design, the accomplishments to date and the most promising areas of research for this class of novel antineoplastic therapies are summarized in this review, with a particular focus on completed or ongoing clinical trials.
