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The Making of Medicine

Discovered: The Oncogene That Causes Glioblastoma

Our Hui Li, PhD, and his collaborators have discovered the gene that causes glioblastoma, a key step toward developing new and better treatments for this deadly brain tumor.

Professor Li said this oncogene (a cancer-causing gene) could be glioblastoma’s “Achilles’ heel” because the tumor cells need it to survive. Blocking the gene’s activity in lab mice eradicated the cancer cells but didn’t affect normal cells. (We all have this gene, called AVIL. It normally helps our cells keep their size and shape, but it goes awry in glioblastoma and helps the cancer form and spread.)

“AVIL is overexpressed in 100% of glioblastoma cells and clinical samples, and is expressed at even higher level in so-called glioblastoma stem cells, but hardly expressed in normal cells and tissues,” Professor Li  said. “Silencing the gene wiped out glioblastoma cells in culture and prevented animal xenografts, while having no effect on normal control cells. Clinically, high AVIL expression correlates with worse patient outcome. These findings and classic transformation assays proved AVIL being a bona fide oncogene.”

The next step is to figure out how to target this gene. Scientists have already developed other targeted cancer treatments using this approach.

“Glioblastoma is one of the most deadly cancers. Unfortunately, there is no effective treatment option,” said Professor Li, of the UVA Cancer Center. “The novel oncogene we discovered promises to be an Achilles’ heel of glioblastoma, with its specific targeting potentially an effective approach for the treatment of the disease.”

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