Until now, stem cells were identified only in aggressive, fast-growing tumors. But a mouse study at Washington University School of Medicine in St. Louis has revealed that slow-growing tumors also have treatment-resistant stem cells. Thus, prompting worries among medical experts that the cells' transformative powers would help cancers escape treatment.
Researchers used a mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumors to identify cancer stem cells and demonstrate that they could form tumors when transplanted into normal, cancer-free mice. Researchers found that the low-grade brain cancer stem cells were less sensitive to anticancer drugs. In the laboratory tests, it took 10 times the dosage of these drugs to kill the low-grade cancer stem cells. As compared with healthy stem cells from the brain, the cancer stem cells made more copies of a protein called Abcg1 that helps those cells survive stress.
David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology and senior author of the study, said, "This protein blocks a signal from inside the cells that should make them more vulnerable to treatment. If we can identify a drug that disables this protein, it would make some cancer stem cells easier to kill. At the very least, we're going to have to use different drugs and different, likely higher dosages to make sure we kill these tumor stem cells."
Researchers said that these findings could be applied more broadly to other brain tumors. Gutmann said, "Because stem cells haven't differentiated into specialized cells, they can easily activate genes to turn on new developmental programs that allow the cells to survive cancer treatments. Based on these new findings, we will have to develop additional strategies to keep these tumors from evading our best treatments."
The research appears online in 'Cell Reports'.