Mounting a strategic offense: fighting tumor vasculature with oncolytic viruses

• Oncolytic viruses can target both tumor cells and the tumor vasculature.
• Oncolytic viruses can be innately antiangiogenic or modified to increase their antivascular effects.
• Combination treatment with antiangiogenic compounds and oncolytic viruses can increase the effectiveness of antitumor therapies.

Blood supply within a tumor drives progression and ultimately allows for metastasis. Many anticancer therapies target tumor vasculature, but their individual effectiveness is limited because they induce indirect cell death. Agents that disrupt nascent and/or established tumor vasculature while simultaneously killing cancer cells would certainly have a greater impact. Oncolytic virotherapy utilizes attenuated viruses that replicate specifically within a tumor. They induce cytotoxicity through a combination of direct cell lysis, antitumor immune stimulation, and recently identified antitumor vascular effects. This review summarizes the novel preclinical and clinical evidence regarding the antitumor vascular effects of oncolytic viruses, which include infection and lysis of tumor endothelial cells, natural or genetically engineered antiangiogenic properties, and combination therapy with clinically approved antivascular agents.