Researchers discover way to inhibit brain cancer’s infiltration mechanism in glioblastoma

A team of experimental oncology 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 4 in 100,000 people, according to Brain Tumor Canada, with an average survival of 12 to 18 months.

The researchers used human cell cultures and mice to investigate the mechanism behind recently discovered tumor microtubes—long protrusions that create a “fiber 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. The study is published in the journal Neuro-Oncology.

“Identifying the main players in the formation of tumor 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 Ph.D. 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 fiber networks to guide migrating neuronal cells to their final destinations. The team found that FABP7 appears to be re-expressed in tumor microtubes, allowing cancer cells to exploit a similar fiber-guided migration mechanism.

By chemically inhibiting FABP7 in cellular experiments, the team was able to prevent the formation of tumor microtubes, reduce tumor 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 tumor 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.

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Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021.

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Andrew Zinin

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