Targeting a pair of enzymes may inhibit the spread of glioblastoma

Glioblastoma is notoriously resistant to modern medicines, spreading to new areas of the brain quickly and resulting in a median patient survival of 14 months from diagnosis. Researchers from the University of Southampton have recently found a possible way to inhibit the growth and spread of the aggressive cancer, making it more susceptible to treatment with the current gold standard of radiotherapy, chemotherapy or surgery.

Sandrine Willaime-Morawek led the study along with her postdoctoral researcher Elodie Siney; they published the results in the journal Molecular Neurobiology.

Glioblastoma has been challenging to treat since it is incredibly resistant to most interventions, in part because most of the tumors house a small population of cancer stem cells (CSCs) that adapt to changes in its microenvironment.

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The researchers first went after the CSCs in an in vitro model of glioblastoma, generating human high-grade glioma sphere-forming cells (GSCs) to look at the migration and adhesion properties of these cells.

The researchers focused on a particular family of enzymes called ADAMs that are highly expressed in glioblastoma. Specifically, ADAM10 and ADAM17 showed the greatest abundance in the tumors. When the scientists inhibited these enzymes, GSC migration increased without affecting healthy neural stem cells. They also found that the migrated GSCs had a differentiated phenotype. The study hints toward the possibility of targeting ADAM10 and ADAM17, drawing GSCs away from the tumor and resulting in a differentiated cell type that is susceptible to treatment with the current gold standard of radiotherapy, chemotherapy or surgery.

"When confirmed in animal models of glioblastoma, this finding will be of great importance for patients and clinicians," said Sandrine in a release. "Glioblastoma is a devastating disease which is often untreatable. We have found that blocking ADAMs may lead to reduced tumor growth and less recurrence following conventional treatments, improving the chance of complete surgical removal and improving survival rates."

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