GLIOBLASTOMA patients have a median survival of 10–12 months due to this aggressive brain cancer, which affects astrocytes, develops rapidly, and recurs often; however, new research from Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA, could be about to change the face of glioblastoma treatment following the discovery of a new experimental, inhibitory compound.
Part of the reason glioblastoma is so deadly is the easy access the affected astrocytes have to the numerous blood vessels of the brain, which enables easy migration and growth of tumours. Additionally, glioblastoma has a high recurrence rate, which is partly influenced by a subpopulation of self-regenerating tumour cells, known as glioma stem cells. Glioma stem cells express high levels of the enzyme CDK5, and previous studies in Drosophila have shown that silencing the CDK5 gene resulted in a decrease in tumour size and the number of glioma stem cells, a fact that the research team from Northwestern University investigated further.
The research team identified that CDK5 promoted a high level of stemness in the tumour population, and through the application of an experimental inhibitor of CDK5, named CP681301, to human glioblastoma cells, the team were able to inhibit tumour growth and reduce the stemness of glioma stem cells. Analysis of the impact of CP681301 on neural, classic, and mesenchymal glioblastoma exhibited varying degrees of success; while neural and classic glioblastoma responded well to the inhibitor, mesenchymal glioblastoma cells were less responsive to CP681301.
CP681301 shows long-term promise for the treatment of glioblastoma, and the future combination of the CDK5 inhibitor with chemotherapy could prove to be a potent treatment for this deadly brain cancer. Study lead, Dr Subhas Mukherjee, Northwestern University, summarised the application of the experimental treatment: “The idea [of the inhibitor] is to kill the [tumour] remnants and glioma stem cells after chemotherapy.” With new studies already being developed, this life-saving therapy could be just around the corner.
