Abstract
Oncolytic viruses (OVs) are a promising type of cancer therapy since they selectively replicate in tumor cells without damaging healthy cells. Many oncolytic viruses have progressed to human clinical trials, however, their performance as monotherapy has not been as successful as expected. Importantly, recent literature suggests that the oncolytic potential of these viruses can be further increased by genetically modifying the viruses. In this review, we describe genetic modifications to OVs that improve their ability to kill tumor cells directly, to dismantle the tumor microenvironment, or to alter tumor cell signaling and enhance anti-tumor immunity. These advances are particularly important to increase virus spread and reduce metastasis, as demonstrated in animal models. Since metastasis is the principal cause of mortality in cancer patients, having OVs designed to target metastases could transform cancer therapy. The genetic alterations reported to date are only the beginning of all possible improvements to OVs. Modifications described here could be combined together, targeting multiple processes, or with other non-viral therapies with potential to provide a strong and lasting anti-tumor response in cancer patients.