The metabolic state of glioma stem cells, which give rise to deadly glioblastomas, is significantly different from that of the brain cancer cells to which they give birth, a factor which helps those stem cells avoid treatment and cause recurrence later.
Researchers with the UCLA Department of Radiation Oncology at UCLA’s Jonsson Comprehensive Cancer Center also found for the first time that these glioma stem cells can change their metabolic state at will, from glycolysis, which uses glucose, to oxidative phosphorylation, which uses oxygen.
The glioma stem cells’ ability to change their metabolic state at will also allow these stem cells that seed new cancer growth to evade treatment and remain alive, said Dr. Frank Pajonk, an associate professor of radiation oncology and senior author of the study.
“We found these cancer stem cells are substantially different in their metabolic states than the differentiated cancer cells they create, and since they act differently, they can’t be killed in the same way,” Pajonk said. “And as yet, we don’t have anything to target these glioma stem cells specifically.”
The study is published this week in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.
Cancer cells take up large amounts of glucose, which fuels their grow and spread, and allows them to be differentiated from normal cells under Positron Emission Tomography (PET) scanning, which captures metabolic activity. Pajonk and his team found that the glioma stem cells took up much less glucose, which makes them difficult to detect with PET.
Targeting cancer metabolic pathways as a treatment has gained new interest in recent years. However, these cancer stem cells that take up less glucose could evade those treatments by utilizing glucose more efficiently through oxidative phosphorylation, which would not be targeted by such drugs.