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Researchers Identify Genes that Allow Cancer Cells to Resist Treatment

After first isolating cancer stem cells in adult brain tumors in 2004, Cedars-Sinai researchers have recently found these cells to be highly resistant to chemotherapy and other treatments. Even if a tumor is almost completely obliterated, it will regenerate from the surviving cancer stem cells and be even more resistant to treatment than before.

Results of studies on three established glioma cell lines and tumor tissue removed from five patients at the medical center appeared in the Dec. 2, 2006 issue of the journal Molecular Cancer. Researchers at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute describe genes and mechanisms that give cancer stem cells their chemo-resistant properties.

"In this study, we provide the first evidence that cancer stem cells have a significant resistance to conventional chemotherapeutic agents. We also link this resistance to genes that are known to inhibit a cell death process called apoptosis," said neurosurgeon John S. Yu, M.D., co-director of the Comprehensive Brain Tumor Program at Cedars-Sinai and senior author of the journal article.

Part of the study included a comparison of cells taken from patients' primary tumors with cells taken from a recurring tumor after radiation, chemotherapy and/or immunotherapy. In each of the five cases examined, the recurrent tumors contained much higher concentrations of cancer stem cells, indicating that while many tumor cells may have died, treatment-resistant "source" cells survived and regenerated.

Another finding suggests that cancer stem cells are responsible not only for regeneration of tumor cells but also encourage their migration. Gliomas are extremely difficult to treat because they evade treatment and are highly invasive.

"The identification and study of brain cancer stem cells are providing insight into how tumors form and grow," said Yu. "This may be a major step toward designing therapies that use brain cancer stem cells as a target, not only to destroy a tumor but to prevent it from coming back."

The study was funded by grants from the National Institutes of Health.

Citation: Molecular Cancer, Dec. 2, 2006, "Analysis of Gene Expression and Chemoresistance of CD133+ Cancer Stem Cells in Glioblastoma."