‘Achilles heel of glioblastoma’: Scientists identify gene responsible for fatal brain cancer

CHARLOTTESVILLE, Va. – Glioblastoma, a common and aggressive type of brain tumor, is always fatal. Most patients die within 12 to 18 months of diagnosis. In a promising new finding, scientists at the University of Virginia say they now know which gene is responsible for this cancer. The discovery offers new hope doctors can eventually develop a treatment.

Specifically, the study pinpoints a type of oncogene known as AVIL. Oncogenes are naturally occurring genes that have the potential to cause cancer. In tumors, oncogenes are commonly mutated or occur at high levels. Consequently, oncogenes are often a target of cancer therapies.

“Glioblastoma is one of the most deadly cancers. Unfortunately, there is no effective treatment option for the disease. The current standard option, radiation plus temozolomide, which displayed a 2.5-month better survival rate, was hailed as a great success,” says researcher Hui Li in a media release.

Finding brain cancer’s ‘Achilles’ heel’

Li says although more research is needed, researchers believe they know where the weak point is in this devastating disease. “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,” Li explains.

The main job of the oncogene AVIL  is to help cells maintain their size and shape. When the gene is overactive, however, it causes the development and spread of cancer cells.

In the study, researchers block AVIL in mice. By doing so, they are able to completely destroy glioblastoma cells.

“AVIL is overexpressed in 100% of glioblastoma cells and clinical samples, and is expressed at even higher levels in so called glioblastoma stem cells, but hardly expressed in normal cells and tissues,” Li adds. “Silencing the gene wiped out glioblastoma cells in culture and prevented animal xenografts, while having no effect on normal control cells.”

The study authors say high AVIL activity is present in the worst brain tumor cases. They add their findings prove AVIL is a “bona fide oncogene.”

A surprise discovery

Interestingly, Li and his team at UVA weren’t even studying glioblastoma when they first began to look at AVIL. They were instead focusing on a rare childhood cancer known as rhabdomyosarcoma.

While studying the cancer, which usually forms in skeletal muscle tissue, researchers found an abnormality in the AVIL gene. This prompted them to look at AVIL in adult cancers. When they did, they found that the gene plays a critical role in glioblastoma.

The UVA team believes finding links between childhood and adult cancers can help the research into more forms of the disease. This is because childhood cancers typically involve fewer mutations than adult cancers, making them easier to understand.

“In this day and age, many people thought that all the significant oncogenes have been discovered. Here we uncovered a novel, powerful oncogene and elucidated its signaling pathways, all starting from studying a structure variant in a pediatric cancer,” says Li.

“In the past, numerous significant discoveries in cancer also stemmed from studying pediatric tumors. We believe this is a strategy that can be applied to find novel players in other adult cancers.”

The study is published in Nature Communications.

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