Creating Viruses That Seek and Destroy the Tumor Program
Clodagh O’Shea, Molecular and Cell Biology Laboratory, Salk Institute
Most cancer patients are treated with non-specific cellular DNA poisons that have devastating side effects and ultimately do not cure patients. Cancer is a complex disease. To conquer cancer requires a therapeutic agent that is as sophisticated as the disease itself. There are few agents on the horizon that have more potential than tumor selective replicating viruses, also known as oncolytic viruses. Viruses are Nature’s nanomachines: their outer coats enable them to enter specific tissues in our body where they express proteins that hijack the cellular growth controls, forcing the cell to replicate and unwittingly reproduce the virus at the same time. The very same cellular growth controls are targeted by mutations in cancer. This overlap can be exploited to engineer viral nanomachines that act like tumor mutation-activated missiles, which specifically replicate in tumor cells and burst them apart to release thousands of virus progeny that seek out and destroy any remaining tumor cells. In clinical trials, the prototypes for such oncolytic nanotherapies have been shown to be safe with evidence of promising activity. Informed by the clinical experience and enabled by the development of new technologies, synthetic viral-based nanomachines can be assembled as intelligent cancer diagnostics and optimized tumor killers. The ultimate goal is for these viral cancer-killing agents to be disguised and deployed in the blood, seek out distant micrometastases and overcome all possible tumor resistance. Such intelligent killers could have a major impact in improving the treatment of patients suffering from cancer.