Stopping the deadly spread of glioblastoma

A team of Terry Fox-funded researchers at the University of Alberta is shedding light on how the deadly brain cancer glioblastoma spreads. In newly published research, they identify a potential treatment target to slow or even stop it.

Glioblastoma is an aggressive form of cancer that affects four in 100,000 people, with an average survival of 12 to 18 months.

The researchers used human cell cultures and mice to investigate the mechanism behind recently discovered tumour microtubes—long protrusions that create a “fibre network” to facilitate rapid invasion of glioblastoma cells into new sites throughout the brain. The microtubes are associated with resistance to both radiotherapy and chemotherapy.

“Identifying the main players in the formation of tumour microtubes may be key to inhibiting glioblastoma cell invasion and therapy resistance,” says Daniel Won-Shik Choi, who was first author on the study as a PhD student in the laboratory of oncology professor Roseline Godbout. 

The team’s research shows that a brain fatty acid-binding protein (FABP7) that is normally present during brain development is overexpressed in glioblastomas. While the brain develops, the FABP7 helps neural stem cells form fibre networks to guide migrating neuronal cells to their final destinations. The team found that FABP7 appears to be re-expressed in tumour microtubes, allowing cancer cells to exploit a similar fibre-guided migration mechanism.

By chemically inhibiting FABP7 in cellular experiments, the team was able to prevent the formation of tumour microtubes, reduce tumour migration and increase sensitivity to temozolomide, a chemotherapy drug. They also treated mice with glioblastoma with the FABP7 inhibitor and found they lived significantly longer than those in the control group.

The Godbout lab is now exploring whether FABP7 inhibition can be effective when combined with standard cancer treatments, such as temozolomide or radiotherapy, in a larger cohort of mice. 

“Our results indicate that tumour microtube formation can be mitigated by FABP7 inhibition with the potential of improving clinical outcomes in glioblastoma patients,” says Choi, who is completing a postdoctoral fellowship at McMaster University and is soon to join the faculty at the University of Saskatchewan.

TFRI funded this research through the Prairie Cancer Research Consortium Pilot for the Marathon of Hope Cancer Centres Network.

Article originally published by the University of Alberta.