For several years, researchers have been working on a new approach to treating cancer, using viruses to infect and kill cancer cells while leaving normal cells unharmed. This approach, called oncolytic virotherapy, has the potential advantage of having low toxicity compared to traditional cancer chemotherapy treatments. Now, researchers at the Mayo Clinic in Rochester, Minnesota, have combined oncolytic virotherapy with antiangiogenic cancer therapies that attack the tumor blood supply to induce substantial regression of tumors in laboratory mice.
Cancerous tumors recruit their own supply of new capillary blood vessels (angiogenesis) in order to grow and spread. One of the critical proteins that promote tumor blood vessel growth, vascular endothelial growth factor (VEGF), is the primary target of drugs used to treat several types of cancer. VEGF stimulates the proliferation of endothelial cells—the cells that line the inner walls of blood vessels. Malignant tumors secrete high levels of VEGF to facilitate the growth of blood vessels that feed the tumor with oxygen and nutrients.
In the new study, researchers found that temporarily stopping anti-VEGF therapy in mice harboring the deadly skin cancer malignant melanoma allowed the blood vessel endothelial cells to be killed by viruses. The transient interruption of antiangiogenic therapy created a “pulse” of rebound angiogenesis by the tumor that allowed the virus to enter and kill both replicating endothelial cells and tumor cells. The treatment also triggered an immune response against the tumor blood vessels.
While combination oncolytic virotherapy and antiangiogenic therapy could theoretically be used to treat a wide range of cancers, the study authors caution that testing of this approach in the clinic will require careful monitoring of possible toxicities to blood vessels in normal tissues.