Some brain tumors are difficult to get rid of and often regenerate following treatment. A group of researchers, however, have identified a way in which brain tumor stem cells – the key to this regeneration – can be disrupted, potentially halting the spread of aggressive cancer.
“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.
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.