By revealing the inner workings of a common cell-to-cell signaling system, University of Michigan biologists have uncovered new clues about mysterious and contentious creatures called cancer stem cells.
The findings also have implications for a high-profile breast-cancer drug trial getting underway at the U-M Medical School and two other institutions.
In the groundbreaking trial, researchers are combining chemotherapy with a drug that blocks the Notch signaling pathway, which helps regulate fetal development and is active in most organ systems throughout a person's life.
The aim is to use so-called Notch inhibitors to attack cancer stem cells, the small fraction of stem cells inside a tumor that help it survive and that fuel its growth.
But a big concern is that the Notch inhibitors, while helping to destroy cancer stem cells, might also kill or harm the normal, healthy stem cells critical to a patient's survival – such as blood-forming stem cells in the bone marrow.
New results from the U-M's Dr. Ivan Maillard and his colleagues may allay some of those fears. The researchers showed that blood-forming stem cells in mice survive just fine when the Notch signaling pathway is experimentally blocked.
"Our data indicate that normal blood-forming stem cells should not be damaged by the Notch inhibitor drug being used in these patients," said Maillard, a hematologist and a Life Sciences Institute researcher.
"That's important, since these patients typically need good blood stem cells to maintain their blood counts and recover from the effects of chemotherapy," he said.
The Notch findings will be published Thursday in the journal Cell Stem Cell. Maillard's team includes researchers from the University of Pennsylvania School of Medicine, the Swiss Institute for Experimental Cancer Research, and Harvard Medical School.
Dr. Max Wicha, director of the U-M Comprehensive Cancer Center, said Maillard's results are welcome news for cancer stem cell researchers, and for the 30-patient metastatic breast-cancer drug trial that launched last month at his center, at the Baylor College of Medicine in Houston, and at the Dana-Farber Cancer Institute in Boston.
"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.