Local research looking at tiny but mighty defense for aggressive tumors

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It’s considered a death sentence. Senator Ted Kennedy knew when he was diagnosed he wouldn’t survive his disease. Glioblastomas mount an indestructible defense. But local researchers are hoping the most aggressive brain tumor will fall to the tiny but mighty nanoparticle.

Northwestern Medicine cancer researcher Alexander Stegh had a target – a faulty gene found in more than 90% of patients with glioblastomas – a lethal and aggressive form of brain cancer. But he didn’t have a tool to fix it.

Alexander Stegh, PhD: “My lab has an interest in identifying genetic aberrations in this gene but we didn’t have the technology to turn this switch off

He partnered with Chad Mirkin – a colleague who had already developed a spherically-shaped nanoparticle – a tiny structure scientists use to deliver therapies to hard-to-reach cells in the body.

Alexander Stegh, PhD: “The really fascinating aspect about this particle is it has the capacity to cross the blood brain barrier and that is a demarcation line that separates the brain, the brain tumor from the body, from the body circulation. It’s a very difficult barrier to overcome.”

The nanoparticles not only made it to the tumor, they engulfed it, infiltrated the cells and turned off the key genetic switch that allowed the cancer to grow.

Alexander Stegh, PhD: “It slows down the growth of the tumor, the tumor cells and makes them again sensitive for therapy to induce tumor cell death.”

It’s promising news. Survival rates among patients with glioblastomas are grim – on average, patients live 14 to 16 months after diagnosis. Surgery, chemotherapy and radiation can help keep the tumor in check but not for long.

Alexander Stegh, PhD: “They grow very invasively so they don’t stay confined to a local tumor mass but they have the capacity to infiltrate normal brain tissue and that makes it difficult for a surgeon to completely resect it so there’s almost always residual tissue and that can flare up and you almost always have recurrent disease.”

Stegh’s experiment was effective in mice with tumors that resembled those found in humans.

Alexander Stegh, PhD: “When we treat these animals we saw a three-fold reduction in tumor size and we saw up to 20% increase in overall survival of mice that bared a human glioma. The next step for us is to develop combination therapies where we use these particles and combine them with first-line chemo and radiation to see if we can further enhance this beneficial effect of these nanoparticles.”

Dr. Stegh is hoping to launch a small clinical trial in late 2014. He’ll test the safety of the particles in humans and determine if they work just as they did in mice.

You can learn more at http://www.northwestern.edu/newscenter/stories/2013/10/incurable-brain-cancer-gene-is-silenced.html

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