Scientists find way to disrupt brain tumor stem 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
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 at Washington University School of Medicine
in St. Louis have identified a key player in that maintenance process.
When the process is disrupted, they found, so is the spread of cancer.
“This discovery may help us attack the root of some of the deadliest brain tumors,” said senior author Albert H. Kim,
MD, PhD, assistant professor of neurological surgery. “A successful
brain cancer treatment will very likely require blocking the tumor stem
cells’ ability to survive and replenish themselves.”
The findings are published online June 11 in Cell Reports.
Kim studies glioblastoma, a deadly form of brain cancer that each
year strikes about 18,000 people in the United States. The average
length of survival after diagnosis is 15 months, and only 30 percent of
patients survive more than two years.
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,” said Kim,
who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
Kim and his colleagues 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,” Kim
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.
Kim’s lab is 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