Repurposing Allosteric Modulators of Glutamate Signalling for Glioblastoma Therapy

Glioblastoma is a highly aggressive form of brain cancer in adults. These cancers are challenging to treat because they become resistant to therapy and this resistance is linked to the fact that the tumour cells are not all the same. For example, some glioblastoma cells connect to each other to form a network, which makes these connected tumour cells more resistant to therapies. Nerve cells from the brain can also connect to this tumour network and inadvertently help glioblastomas to grow. 

The communication between nerve cells and glioblastoma require certain proteins (called glutamate receptors) that allow glioblastomas to ‘read’ the signals from the nerve cells. Our experiments suggest that glioblastomas make glutamate receptors that are different from those found in the normal brain.

In this project, we will test if glioblastoma glutamate receptors can be targeted by drugs called ‘negative allosteric modulators’, or NAMs, to prevent glioblastoma growth.  We will try to develop new NAMs that act against glioblastoma without affecting glutamate receptors in the normal brain, which should have fewer side effects than currently existing drugs. 

If successful, we want to develop NAMs as glioblastoma therapies in the future.