There is a huge need for better treatment options for the aggressive brain cancer, glioblastoma (GBM) as the five-year survival rate is only 5% to 10%. In addition, tumour growth is often enabled by the formation of new blood vessels to provide oxygen and nutrients. Drugs directed against VEGF or VEGFR inhibit this process. However, these drugs have proven to be less effective in GBM.

A team from the University of Pennsylvania has demonstrated that targeting a mechanism in endothelial cells that line the inside of blood vessels, could help overcome drug resistance in GBM. The team found that a mechanism within the well-known Wnt/β-catenin signalling pathway causes endothelial cells to act more like stem cells (stemness-like activation), leading to an abnormal growth of blood vessels that makes brain cancer cells resistant to treatment.

In a mouse model, β-catenin inhibition sensitized GBM to cytotoxic treatment, suggesting that combining cytotoxic therapy with Wnt signalling inhibition might overcome pharmacoresistance in GBM, according to the recent study published in Science Translational Medicine.