INVESTIGATING NEW DRUGS FOR THE TREATMENT OF CHILDHOOD EPENDYMOMA

Ependymoma is a type of brain tumour that usually affects children, and develops from the cells lining the fluid-filled spaces in the brain called ventricles. Following treatment, this type of tumour often returns in a treatment-resistant form.

In this project,  Professor Grundy and his team are testing drugs called ‘histone deacetylase inhibitors’ (HDACi) on ependymoma cells. These drugs are designed to re-activate the body’s natural defence mechanisms against brain cancer.  Normal, healthy cells use ‘tumour suppressor genes’ to help control their growth.  In certain ependymoma cells, however, some of these genes are de-activated by proteins called histone deacetylases, allowing the cells to grow and multiply in an uncontrolled way. The HDACi drugs could help to stop this process.                   

Previous lab work by the group has shown that the HDACi ‘Trichostatin A’ causes most ependymoma cells to grow more slowly and to eventually die. One HDACi is currently being trialled in the treatment of adult patients with another type of brain tumour, glioblastoma multiforme.

It is hoped that this research, which The Joseph Foote Trust is jointly funding with the Samantha Dickson Brain Tumour Trust, will lead to a better understanding of the biology of the cancer cells that return following initial treatment, and of the factors responsible for their resistance to therapy. This could lead to new ways to predict how these tumours will behave, and how ependymoma cells can be targeted and destroyed by new cancer drugs.

We are making best use of the huge amount of data we have now generated from our in depth studies of Children’s Brain Tumours. We are also developing model systems of childhood brain tumours in order to better understand where they come from and understand how they become drug resistant, and how to improve our treatments. 

Professor Richard Grundy, University Nottingham