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Two Genes Work in Tandem to Spur Deadliest Brain Cancer

Scientists discover the duo turns on hundreds of other genes that help disease spread

WEDNESDAY, Dec. 23 (HealthDay News) -- Two genes working in concert seem to spur the deadliest form of brain tumor, glioblastoma, the disease that took Sen. Ted Kennedy's life last August.

Scientists reporting in the Dec. 23 online edition of Nature said that the dynamic duo of genes are turned on in about 60 percent of patients with glioblastoma, and that those patients have an especially bad prognosis.

"We discovered that tumors expressing these two genes displayed much worse clinical outcomes. This is remarkable given that it's based on [just] the activity of two genes," said study senior author Dr. Antonio Iavarone, an associate professor of neurology at Columbia University Medical Center's Herbert Irving Comprehensive Cancer Center in New York City.

"These researchers have identified two transcription factors that appear to be causative. They're not just markers. They appear to actually cause the tumor," added Dr. Todd Waldman, an associate professor of oncology at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C. "For brain tumors, it's very exciting because it helps to explain why they are so devastatingly infiltrative."

Zeroing in on such specific targets brings the possibility of new therapies closer to the realm of reality.

"We are now trying to identify new compounds to block the function of the proteins," added Iavarone. "Some may be already available in the chemical library. We're in good shape because we know what we want to find, we know what the drug should do."

Glioblastomas multiforme -- dubbed "The Terminator" by one group of researchers -- are devastating because they so easily and quickly invade healthy brain tissue surrounding the tumor.

Scientists have been trying without huge success to understand why these tumors are so wildly aggressive.

Iavarone and colleagues determined that each of these newly identified genes -- C/EPB and Stat3 -- caused little damage on their own but, in tandem, wreaked havoc by switching on hundreds of other genes.

After almost a year, all patients in the study who had both genes turned on had died versus only one-half of those who had different types of tumors.

"These are not markers but master regulators of the most aggressive phenotype of brain tumor," Iavarone said. "Markers can tell us certain features of tumors but they're not the real engine behind the tumors. We have found the real driver making the tumors."

Turning off the genes in human brain tumor cells rendered them incapable of forming tumors when injected into mice.

More information

The U.S. National Cancer Institute has more on brain tumors.

SOURCES: Antonio Iavarone, M.D., associate professor, neurology, Columbia University Medical Center's Herbert Irving Comprehensive Cancer Center, New York City; Todd Waldman, M.D., Ph.D., associate professor, oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C.; Dec. 23, 2009, Nature, online

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