Unwrapping genes to find new treatments

Fast facts

• Official title: Tumours of the nervous system: from biology to therapy
• Lead researchers: Professor Daniel Hochhauser and Professor Paolo Salomoni
• Where: Samantha Dickson Brain Cancer Unit, University College London
• When: October 2009 – March 2019
• Cost: £2.3 million
• Research type: Adult, High Grade, Tumour biology, Academic

Investigating how tumour cells produce energy and package up their DNA to find new treatment targets for high grade glioma.

Researchers at University College London will be studying the interplay between a cell’s metabolism and the way DNA is packaged to identify how high grade gliomas form and discover new treatments.

High grade gliomas are very aggressive and have a poor prognosis. The researchers want to understand what causes this aggression and how this leads to therapy resistance.
The team at UCL, led by Professor Paolo Salomoni, will be investigating how mutations to a protein known as histone H3.3 lead to tumour development, and how this is linked to mutations to an enzyme called IDH1.

IDH1 has a role in the cell’s metabolism – the process that generates energy, and mutations to the enzyme have been linked to high grade glioma. The researchers will be investigating the idea that changes to the cell’s metabolism alter the way that histone proteins package DNA. Through packaging DNA, histone proteins send ‘messages’ that control which genes are switched on and off.

The team will determine whether IDH1 and histone H3.3 can act as drug targets and hope that this work will lead to clinical trials.

The researchers will also be investigating autophagy, a process of cell degradation that also has a role in energy production. Alterations to autophagy can allow tumour cell survival, leading to resistance to therapy. Research into autophagy at UCL has already led to clinical trials investigating whether the anti-malarial drug hydroxychloroquine can target the autophagy pathway and prevent drug resistance.

This study is being carried out as part of a £1.5 million five year research programme at The Samantha Dickson Brain Cancer Unit at the UCL Cancer Institute. By investigating the biological mechanisms behind high grade glioma, the team hope to identify new drug targets, leading to targeted treatments to be used in clinical trials.