Stem cells have the remarkable ability to transform into any cell type in the body, and scientists have long been fascinated by this "superpower." However, this same potential can be a double-edged sword, especially in the context of cancer treatment. Researchers now believe that cancer stem cells—found in malignant tumors—may play a key role in helping cancer resist therapy. A groundbreaking new study reveals that the threat posed by these cells is even greater than previously thought.
Previously, scientists only recognized stem cells in fast-growing, invasive tumors. But a team from the University of Washington discovered that slow-growing tumors also contain dangerous stem cells. These low-grade cancer stem cells are highly resistant to standard chemotherapy, according to research published in *Cell Reports* on March 12. The findings challenge previous assumptions about where and how cancer stem cells operate.
The researchers compared these cancer stem cells with normal stem cells and uncovered their unique mechanisms for evading drug treatments. "To effectively target these cells, we may need to increase the dosage or use different drugs," said Professor David H. Gutmann, one of the study's authors. Dr. Yi-Hsien Chen, the first author, developed a mouse model for NF1-related low-grade brain tumors. He identified cancer stem cells in this model and showed that they could form tumors in healthy mice.
NF1, or neurofibromatosis type 1, affects approximately one in every 2,500 babies. It can lead to various complications, including brain tumors, vision loss, learning disabilities, behavioral issues, heart defects, and skeletal abnormalities. Optic gliomas are the most common brain tumors in children with NF1, often requiring treatment with drugs that target cell growth pathways.
In this study, it was found that ten times the usual dose of these drugs was needed to kill low-grade cancer stem cells. Further experiments revealed that these stem cells produce higher levels of the Abcg1 protein compared to healthy brain stem cells. This protein helps them survive under stress, and it blocks an internal signaling pathway, making them less responsive to treatment. "If we can find a drug that inhibits Abcg1, we can make it easier to eliminate these cancer stem cells," explained Gutmann.
While the study focused on NF1-related optic gliomas, the researchers believe the findings may apply to other types of brain tumors as well. "Since stem cells haven't fully differentiated, they can activate new genes that help them survive during cancer treatment," Gutmann noted. "We need to develop better strategies to target them."
Author: Yi-Hsien Chen
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