A team of researchers from Northwestern University, USA have identified a molecule that could be used to inhibit the growth of the most fatal paediatric brain tumour, diffuse midline glioma (formally called DIPG).
DIPGs originate in an area of the brain, and more specifically the brainstem, called the pons. The pons is an area deep within the lower part of the brain which is responsible for a number of critical bodily functions, such as breathing, sleeping and blood pressure.
Currently the standard treatment for DIPG is radiotherapy but unfortunately this shows little benefit for children. Therefore new treatment options for this tumour are desperately needed to prolong survival.
Research has shown that 80% of these tumours have a defect in an important protein called a histone. Histones package our DNA into small structural units and regulate gene expression. This research team were the first to show that the histone mutation present (called H3K27M) triggers a biochemical process that turns on cancer promoting genes, leading to the development of DIPG. This vital discovery presented as an ideal target for an investigational drug known to stop this 'turning on' of genes.
The drug used, known as a BET bromodomain inhibitor, prevents the interaction between a tumour causing protein and the mutant histone H3K27M. This in turn forces the tumour cells to differentiate into other types of cells instead, successfully halting tumour growth.
"In this study we successfully targeted histone acetylation with a bromodomain inhibitor, a compound that is currently in studies for different types of advanced cancers in adults, but has never been studied in DIPG," said senior author Ali Shilatifard, PhD, Chair of Department of Biochemistry and Molecular Genetics and Robert Francis Furchgott Professor at Northwestern University Feinberg School of Medicine.
"We were able to show that it kills tumour cells in culture and shrinks the tumour in a mouse model of DIPG. These are very exciting results that we hope will be valuable for children with DIPG. A clinical trial is our next step."
This research is a huge step in the direction of finding a new treatment for this devastating brain tumour. The team hopes to open a Phase 1 clinical trial at Lurie Children's Hospital of Chicago, USA to test the effectiveness and side effects of the drug in a small group of patients.
The target being explored in this study is also being researched by the Structural Genomics Consortium (SGC), who we have partnered with to unlock information about important proteins involved in the development of brain tumours.
The SGC aims to address the structural and functional roles of BET proteins in initiating tumour growth by establishing the network of their interactions. Research of this type will help demystify why cells grow uncontrollably and to help design drugs that aim to target BET proteins, providing a new treatment option for brain tumour patients.
Read more about our partnership with the SGC