Gene Discovery Boosts Brain Cancer Research

WEDNESDAY, Feb. 14 (HealthDay News) -- Researchers have discovered that a gene that triggers the growth of stem cells during early brain development is also key to the growth of deadly adult brain tumors called gliomas.

The protein produced by the gene, called Olig2, "has both Jekyll and Hyde functions," said lead researcher Dr. David H. Rowitch, a professor of pediatrics and neurological surgery at the University of California, San Francisco, Children's Hospital.

"It is very important for some of the repair functions of the brain in some diseases, but it seems to be co-opted by brain cancer stem cells," he said.

Olig2 "is specific to growth in the brain, and if you are able to target the activity of this gene, you might have something that would specifically work on cells in the brain but not have the adverse side effects in the rest of the body," Rowitch said.

In experiments on mice, his team found that blocking the function of the protein almost completely stopped the gliomas from forming. That means that drugs that targeted Olig2 might kill tumor cells without affecting healthy brain tissue, the researchers say.

Their report is published in the Feb. 15 issue of Neuron.

About 10,000 Americans are diagnosed with gliomas each year. "It's a leading cause of cancer-related deaths because there is so little you can do to prevent the rapid progression of this cancer," Rowitch said.

"Glioblastoma is really a pretty dreadful tumor with very few treatment options," agreed William C. Phelps, the Scientific Program Director at the American Cancer Society. "Nothing has shown to be particularly effective, and treatment options have barely changed in the last couple of decades. Treatment is entirely palliative. There is no real effect other than just extending survival for a period of time." he said. "Typical survival is a year."

By looking at human gliomas, Rowitch and colleagues found that Olig2 is activated in the stem cells and growth cells that are found in brain tumors. In experiments with mice that had malignant gliomas, they found that inhibiting Olig2 function stopped tumors from growing in 91 percent of the mice.

The Olig2 gene is critical in the early embryo for the production of all motor neurons, Rowitch said. "Animals that have a mutation of this gene are entirely paralyzed and die at birth," he said. In adults, Olig2 is necessary to the process of repairing brain cells, such as in multiple sclerosis, he noted.

Rowitch's colleague, Charles D. Stiles, a professor of microbiology and molecular genetics at Harvard Medical School, believes that Olig2 may be a good target for brain cancer therapy, since its activity is limited to the brain, and therapy is unlikely to produce adverse side effects elsewhere in the body.

"The charm of Olig2 is that it is confined to the brain," Stiles said. "Although you need Olig2 to develop a brain, and perhaps you need Olig2 to repair certain lesions in the brain, you can go for quite some period of time without Olig2 once the brain has been developed."

Targeting Olig2 as a treatment for brain cancer is still a decade away, Rowitch said. "But I am hoping that this work will lead to an era of targeted therapy for brain cancer."

One expert applauded the research.

"This is a beautiful study showing that the pathways that control normal brain development are the same pathways that are corrupted in gliomas," said Russ Pieper, director of basic science at the University of California, San Francisco, Brain Tumor Research Center.

This paper is among the first to begin to unravel how neural stem cells can contribute to glioma formation and to identify specific genes and pathways involved, Pieper said. "The study further cements the idea that alterations in stem cell differentiation give rise to gliomas, and that this population of cells represents the key therapeutic target," he said.

No drugs currently exist that can target the Olig2 gene, Pieper said. "However, this study will likely spur further investigation into how Olig2 is turned on and how this can be prevented," he said.

More information

For more information on brain cancer, visit the American Cancer Society.

<-Study Sheds Light on Genetics of Colorectal Cancer   ->Five Reasons to Get Off the Couch in '07
Exercise