Attacking Cancer Stem Cells in the Brain

Many types of cancer have been shown to be driven by the existence of a small population of cancer stem cells. This is what leads to the recurrence of cancer following apparently successful treatments to remove tumors, for example: therapies targeting cells making up the bulk of the cancer may not be effective in clearing out the cancer stem cells. On the other hand for cancer types wherein cancer stem cells can be clearly identified, there is an opportunity to strike at the root by attacking these cells:

Some brain tumors are notoriously difficult to treat. Whether surgically removed, zapped by radiation or infiltrated by chemotherapy drugs, they find a way to return. The ability of many brain tumors to regenerate can be traced to cancer stem cells that evade treatment and spur the growth of new tumor cells. But some brain tumor stem cells may have an Achilles' heel, scientists have found. The cancer stem cells' remarkable abilities have to be maintained, and researchers have identified a key player in that maintenance process. When the process is disrupted, they found, so is the spread of cancer.

Scientists have realized in recent years that some cancer cells in glioblastomas and other tumors are more resistant to treatment than others. Those same, more defiant cells also are much better at re-establishing cancer after treatment. "These tumor stem cells are really the kingpins of cancers - the cells that direct and drive much of the harm done by tumors." Researchers identified a protein, known as SOX2, that is active in brain tumor stem cells and in healthy stem cells in other parts of the body. The researchers found that the tumor stem cells' ability to make SOX2 could be turned up or down via another protein, CDC20. Increasing SOX2 by boosting levels of CDC20 also increased a tumor's ability to grow once transplanted into mice. Eliminating CDC20, meanwhile, left tumor stem cells unable to make SOX2, reducing the tumor stem cells' ability to form tumors. "The rate of growth in some tumors lacking CDC20 dropped by 95 percent compared with tumors with more typical levels of CDC20."

When the scientists analyzed human tumor samples, they found that a subset of patients with glioblastomas that had the highest CDC20 levels also had the shortest periods of survival after diagnosis. The researchers are exploring methods to block CDC20 in brain tumors, including RNA interference, an approach in which the production of specific proteins is blocked. That general approach is in clinical trials as a therapy for other cancers, viral infections and other illnesses.

Link: http://news.wustl.edu/news/Pages/Scientists-find-way-to-disrupt-brain-tumor-stem-cells.aspx

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