Some brain tumours are difficult to treat. Whether surgically removed, treated by radiation or infiltrated by chemotherapy drugs, they can find a way to return. The ability of many brain tumours to regenerate can be traced to cancer stem cells that evade treatment and spur the growth of new tumour cells.
But some brain tumour stem cells may have a weakness, scientists have found, and reported in Cell Reports. The cancer stem cells’ abilities have to be maintained, and researchers at Washington University School of Medicine in St Louis, USA, 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 tumours,” said senior author Albert H Kim, assistant professor of neurological surgery. “A successful brain cancer treatment will very likely require blocking the tumour stem cells’ ability to survive and replenish themselves.”
Kim’s focus is on glioblastomas. Scientists have discovered in recent years that some cancer cells in glioblastomas and other tumours are more resistant to treatment than others. Those same, more defiant cells also are better at re-establishing cancer after treatment.
“These tumour stem cells are really the kingpins of cancers—the cells that direct and drive much of the harm done by tumours,” said Kim, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, USA.
Kim and his colleagues identified a protein, known as SOX2, that is active in brain tumour stem cells and in healthy stem cells in other parts of the body.
The researchers found that the tumour stem cells’ ability to make SOX2 could be modified using another protein—CDC20. Increasing SOX2 by boosting levels of CDC20 also increased a tumour’s ability to grow once transplanted into mice. Eliminating CDC20, meanwhile, left tumour stem cells unable to make SOX2, reducing the tumour stem cells’ ability to form tumours.
“The rate of growth in some tumours lacking CDC20 dropped by 95% compared with tumours with more typical levels of CDC20,” Kim said.
When the scientists analysed human tumour 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 tumours, 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.