Glioblastomas are the most common and aggressive form of brain tumors and are known to have a typically poor prognosis.
In disrupting the cancer stem cells'
regeneration process, the researchers at Washington University School
of Medicine in St. Louis, MO, discovered that the spread of cancer is also disrupted.
"This discovery may help us attack the root of some of the deadliest
brain tumors," says senior author Dr. Albert H. Kim, 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."
One of the deadliest forms of brain cancer is glioblastoma, a form also
known as "grow-and-go tumors" that develops in around 18,000 people in
the US every year.
Prognosis is often not good for patients with glioblastomas, with the
average length of survival after diagnosis 15 months. Only 30% of
patients with glioblastomas survive for more than 2 years.
Glioblastomas are typically treated with surgical resection. There is
evidence that the more of a tumor that can be removed, the better the
clinical outcome for the patient, but it can be difficult to remove
large tumors while sparing brain function.
Scientists have recently understood that certain cells in glioblastomas
and other tumors are also more resistant than others to the effects of
surgery, radiation or chemotherapy drugs. It is these specific stem cells that are key to the regeneration of tumors following courses of treatment.
"These tumor stem cells are really the kingpins of cancers - the cells
that direct and drive much of the harm done by tumors," Dr. Kim
explains.
But despite their durability, the tumor stem cells may have a weakness
in their reliance on a protein called SOX2. This protein is active in
both brain tumor stem cells and healthy stem cells located elsewhere in
the body.
Reducing CDC20 levels also reduced tumor growth
Dr. Kim and his colleagues discovered that they could alter the ability
of tumor stem cells to make SOX2 using another protein, CDC20.
Increasing levels of CDC20 in turn increased levels of SOX2, while
eliminating CDC20 entirely meant that the tumor stem cells were unable
to produce SOX2 at all.
The levels of SOX2 influenced the tumor stem cells' ability to grow and
form new tumors when transplanted into mice. Boosting the levels of SOX2
increased the tumor's ability to grow, with the opposite occurring when
SOX2 levels were low.
"The rate of growth in some tumors lacking CDC20 dropped by 95%
compared with tumors with more typical levels of CDC20," said Dr. Kim.
After analyzing a selection of human tumor samples, the researchers then
discovered in a group of patients with glioblastomas that those with
the highest levels of CDC20 also had the shortest periods of survival
after having their cancer diagnosed.
Following these discoveries, the team is now investigating ways to block
CDC20 in brain tumors. One approach being explored is ribonucleic acid
(RNA) interference, a technique that blocks the production of specific
proteins that is currently being used in clinical trials as a form of
treatment for several different illnesses, including some cancers.
The study is published in Cell Reports and supported by funding
from the National Institutes of Health (NIH), the American Cancer
Society, Voices Against Brain Cancer, the Elsa U. Pardee Foundation, the
Concern Foundation and the Duesenberg Research Fund.
This is not the first study in recent months to discover a possible weakness in glioblastoma cells. Previously, Medical News Today reported on a study that found blocking production of an enzyme called GLDC in a subset of glioblastoma stem cells could kill off brain tumors.
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