Unconventional warfare against cancer

K. Ozduman

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Glioblastoma is a brain tumor so fearsome that oncologists call it "the terminator." Traditional surgery and chemotherapy are ineffective against it, and 75 percent of patients die within two years of being diagnosed. But medical school neurosurgery professor Anthony van den Pol ’77PhD aims to curb this cancer's deadly reputation by using a guided missile. Along with his Yale colleagues, van den Pol has generated a virus that targets and kills glioblastoma cells while leaving surrounding healthy tissues unscathed.

Pressing viruses into service as cancer fighters might seem counterintuitive -- many viruses are, after all, disease-causing agents -- but van den Pol recognized therapeutic potential in one of their defining characteristics: an ability to initiate biological change on the cellular level. His team tested about a dozen viruses thought to infect cancer cells; the vesicular stomatitis virus (VSV), a bug that causes stubborn mouth sores in livestock, soon emerged as the most promising candidate.

To evaluate its effectiveness, van den Pol used a virus modified to express a green fluorescent protein and injected it into mice whose brains had been seeded with human glioblastoma cells. Right away, patches of fluorescence spread in cancerous regions of the mouse brains, showing that the virus was doing its work. "Within a few days, the majority of the brain tumors were completely infected with the virus, the tumor cells were dying, and there was minimal infection of the rest of the brain" during the experiments, van den Pol says. (The study appeared in the February Journal of Neuroscience.)

If the safety of the virus can be shown, van den Pol hopes to start testing this treatment in humans within the next few years. There are many regulatory hurdles to be cleared, but he thinks his unorthodox treatment could provide the best hope for patients who are otherwise out of options. "I get a lot of correspondence from people asking if there are clinical trials for this," he says.