"It's really important, because a lot of what we're thinking about now, therapeutically, is trying to find ways to attack these cancer stem cells, because we think that's really what drives the malignancies," said Wicha, who was not involved in the Notch study.
"Ivan's paper, combined with our own work, shows that there may be differences between normal stem cells and cancer stem cells, and perhaps those differences can be exploited therapeutically," Wicha said.
The cancer stem cell theory is controversial. Some researchers are not convinced that cancer stem cells exist.
The current two-stage drug trial uses a Notch inhibitor originally developed by Merck for Alzheimer's patients in the late 1990s, followed by chemotherapy. The intent is to use the Notch inhibitor to make cancer stem cells sensitive to the chemotherapy---a one-two punch to knock out tumors.
If the treatment is effective, the results could help sway some cancer-stem-cell skeptics.
The Notch pathway sends signals from a cell's surface membrane into its nucleus. Those signals activate genes that instruct the cell to make proteins that perform various tasks.
In the lab, Maillard and his colleagues were able to prevent Notch signals from activating mouse target genes using two independent techniques.
Many scientists have long assumed that blood-forming stem cells need Notch signals to function properly. But Maillard's team found that the signals are not required for the maintenance of blood-forming stem cells in adult mice.
|Contact: Jim Erickson|
University of Michigan