Researchers at the University of Florida have discovered the pathway involved in the spread of the most deadly kind of brain cancer. The finding may help physicians pinpoint the cancer earlier on and make better decisions when treating the cancer. It will also allow researchers the ability to target therapeutic drugs in about half of all patients diagnosed with the form of brain cancer, known as "glioblastoma".
“Glioblastoma is the worst type of brain cancer, and also the most common brain cancer in adults,” said Siebzehnrubl, a professor in UF’s Evelyn F. & William L. McKnight Brain Institute. “There is no cure and the prognosis is poor, mainly because the cancer cells can quickly infiltrate the entire brain.”
These cells also resist chemotherapy, so even if surgery and irradiation eradicate the initial tumor, patients often suffer a recurrence of cancer soon after.
The researchers have found a molecular pathway, called the ZEB1 pathway, that, when present, causes cells to leave the initial tumor site, generates resistance to chemotherapy in these cells and generates new tumors away from the initial site.
“ZEB1 is known to be important in a number of cancers, functioning at the level of cancer stem cells, but there has been little work on this transcription factor in brain cancer,” said David Sandak, vice president of Accelerate Brain Cancer Cure. “We are excited about the finding as it integrates a single regulatory pathway with multiple oncogenic mechanisms and provides promise for a new therapeutic target for glioma.”
In patients who have this pathway, the course of the illness is much worse than in those where the pathway is not seen, Siebzehnrubl said. These patients get sick very quickly, don’t respond to chemotherapy and die sooner than those who lack the pathway.
The key regulator appears to be a protein called ZEB1 that binds to specific DNA sequences to control the flow of genetic information that drives this pathway. This particular kind of protein does not a have a specific site where therapeutic drugs can bind, so the researchers must look elsewhere to see if they can target a molecule that activates the pathway farther upstream.
“This gives us an idea of what we can do to target these lethal cells,” Siebzehnrubl said.
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