Combined Effect of Two Genes Lead to Aggressive Brain Cancers

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The most aggressive form of brain cancer has been linked to two genes, according to a study lead by a team of Columbia scientists.

For the study, led by Antonio Iavarone, MD, associate professor of neurology in the Herbert Irving Comprehensive Cancer Center, and Andrea Califano, PhD, director of the Columbia Initiative in Systems Biology, researchers focused their study on glioblastoma multiforme, a condition that is lethal because it rapidly invades the normal brain and produces inoperable brain tumors.

After assembling and experimentally validating a cellular network for a gliobastoma cell, the team was able to identify which genes were responsible for the most deadly features of the tumors. “We now know that two genes—C/EPB and Stat3—are the disease's master ‘control knobs'” said Dr Iavarone. “When simultaneously activated, they work together to turn on hundreds of other genes that transform brain cells into highly aggressive, migratory cells.”

Researchers reported that all patients in the study whose tumors showed activation of both factors died within 140 weeks after diagnosis, while one-half of the patients without these factors were still alive.

“This finding means that suppressing both genes simultaneously, using a combination of drugs, may be a powerful therapeutic approach for these patients, for whom no satisfactory treatment exists,” said Dr Califano.

The findings were published in Nature (2009 Dec 23. [Epub ahead of print]).
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