Linking glioblastomas to DNA-protein parcels

Fast facts

• Official title: Chromatin proteins as drug targets for glioblastoma
• Lead researcher: Professor Steve Pollard
• Where: MRC Centre for Regenerative Medicine, University of Edinburgh
• When: September 2016 – August 2022
• Cost: £1,481,356 over six years
• Research type: Adult, Glioblastoma (High Grade), Academic
• Award type: Quest for Cures

---

What is it?

Previous research has shown that glioblastomas have defects in the mechanisms that control whether key genes are turned ‘on’ or ‘off’. Professor Steve Pollard, in collaboration with scientists from Toronto and Copenhagen, is focusing on these defects, with a particular emphasis on frequent disruptions made in a family of proteins called chromatin regulators, to see how they could be linked to tumour growth.

Chromatin regulators control gene expression. These proteins regulate the entire process of DNA being wrapped tightly into condensed structures called chromosomes.

Chromatin regulators carry the important genetic information that controls how the cells in our body behave. If these regulators become mutated, it changes the way the DNA is wrapped, causing the cell to behave differently.

Professor Pollard’s team will be using the very latest genome editing tools to further their understanding of how these mutations arise and how they affect tumour growth. They’ll particularly look at Trithorax group proteins (a chromatin regulator) and aim to identify which of the 1,000 chromatin regulators should be prioritised for drug development.

They’ll also test drugs that have already been approved for use in other human diseases to see if they can target the chromatin regulators. As these drugs have already been approved for use in humans, they’d can reach brain tumour patients much faster.

Why is it important?

Glioblastomas are the most common, high grade primary brain tumour in adults. With less than 5% of people surviving for five years or more after their diagnosis, the prognosis for this tumour type is dismal. Effective treatment options for these highly aggressive tumours is lacking, which is why we urgently need more research on this tumour type.

There are ongoing efforts to develop new anti-cancer drugs targeting chromatin regulators. So this research project is critical in helping us further our understanding of how these proteins drive glioblastomas and how we can block them.

Who will it help?

This programme of research brings together world-class international researchers with a wealth of expertise in genetics, biochemistry and drug discovery. The strengths and knowledge of the scientists and clinicians involved will drive new discoveries and rapid clinical translation of treatments for glioblastoma. Together, this will ultimately help to improve survival and treatments for people with a brain tumour.

Milestones

2016-2020

• The research team have created and optimised all the lab techniques that are needed for this research project.
• The team have screened for chemical and genetic compounds to find potential new drugs and identified a type of drug called HDAC inhibitors.
• The team have discovered new gene regulators and how they bind to their target.

2020-2022

• Discovered a new metabolic pathway influencing quiescence and epigenetics of genes.
• Found that some Glioblastoma patients have a protein called TAK1 that controls cell death. This is important as it relates directly to the immune system.
• In aggressive tumours, the immune system attempts to fight the tumour, but eventually fails. This is when TAK1 becomes a potential target for treatment, especially in recurrent tumours.

If you have any questions about this, or any of our other research projects, please contact us on [email protected]