With current treatments, approximately 60 to 70 percent of patients live at least five years, but often they are left with cognitive disabilities from surgery, chemotherapy and radiation, urgently suggesting a need for new, more-selective therapies.
"Medulloblastoma was one of the first tumors that was believed to fit the hypothesis that tumors are caused by 'cancer stem cells' that initiate malignancies and sustain them," said Ligon, who is also on faculty and an assistant professor at Harvard Medical School. "But the prevailing hypothesis -- that medulloblastomas originate from non-stem cells just did not make perfect sense with this."
The discoveries emerged from a series of experiments begun in the Rowitch Laboratory at Dana-Farber. The initial goal was to determine whether activating the Sonic hedgehog cancer pathway in multiple types of brain cells, including neural stem cells, could help pinpoint which cells brain cancers might come from. Surprisingly, the scientists generated just one tumor type, medulloblastoma, regardless of whether they activated the pathway in stem cells for other cell types called neurons and glia. This was a surprise: it had been thought that medulloblastoma arose purely from neuronal ("thinking") cells and not "glial" or supporting cells.
An intriguing question for the investigators is why these cells, known as granule neuron precursors, seem to be uniquely vulnerable to the tumor-triggering effects of the Sonic hedgehog pathway, while other brain stem and progenitor cells are not.
Explained Rowitch: "There must be susceptibility factors in the granule neuron precursor cell that predispose it to forming cancer, so we now must try to understand what it is about this c
|Contact: Bill Schaller|
Dana-Farber Cancer Institute