Scientists have identified two genes that, when simultaneously activated, spur the most aggressive forms of human brain cancer.
The discovery, by a team of Columbia scientists led by Antonio Iavarone, associate professor of neurology in the Herbert Irving Comprehensive Cancer Center, and Andrea Califano, director of the Columbia Initiative in Systems Biology, may lead to completely novel strategies to diagnose and treat these incurable tumours.
The researchers studied a type of human malignancy, called glioblastoma multiforme, which is among the most lethal because it rapidly invades the normal brain producing inoperable brain tumours.
Before this study, cancer researchers had little idea why glioblastoma is so aggressive.
"We now know that two genes - C/EPB and Stat3 - are the disease's master 'control knobs'. When simultaneously activated, they work together to turn on hundreds of other genes that transform brain cells into highly aggressive, migratory cells," said Iavarone.
The two genes are active in about 60 percent of all glioblastoma patients and help identify poor-prognosis patients.
All patients in the study whose tumours showed activation of both factors died within 140 weeks after diagnosis, while one half of the patients without these factors were still alive.
Califano said: "The 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."
This approach, called combination therapy, is supported by this study since silencing both genes in human glioblastoma cells completely blocked their ability to form tumours when injected in a mouse.
The findings will be published in an advanced online edition of Nature on Dec. 23, 2009.