Max Tang is a 5th year medical student at the University of Heidelberg. In this vlog Max gives an overview about the research he is doing that is part of the overall EVEREST grant that is funded by The Brain Tumour Charity.
Located across three institutions, the Everest Centre for Research into Paediatric Low Grade Brain Tumours is a groundbreaking international research initiative bringing together experts from Germany and the UK.
Led by Dr David Jones, the research aims to propel our understanding and improve treatment for low grade brain tumours, which can often cause severe long-term health problems and in some cases can be fatal.
The international team will focus on four interrelated streams of research:
1. Determining the origin of low grade brain tumour types
Key researchers: Dr Tom Jacques, University College London; Dr David Capper, Charité Universitätsmedizin Berlin
Low grade brain tumours can be caused by various changes to an individual's genetic code. The research team will use molecular diagnostics to trace the tumour's 'cell of origin'. This will help create a classification system to enable researchers to better target treatments to the individual's specific alterations.
2. Developing low grade brain tumour models and pre-clinical screening
Key researchers: Dr David Jones, German Cancer Research Centre, Germany; Prof JP Martinez-Barbera, University College London, UK
Low grade brain tumours have been notoriously difficult to replicate in the lab. Experts in Heidelberg and London will develop new, more accurate tumour models to test new drugs and drug combinations.
3. Identifying factors that affect tumour growth
Key researchers: Prof Denise Sheer, Queen Mary University London, UK; Prof Stephan Pfister, German Cancer Research Centre, Germany
The growth environment of low grade brain tumours is of great importance, especially as the immune system plays a vital role in regulating tumour growth via what's known as the “oncogene-induced senescence" mechanism. This mechanism suppresses tumour growth and could lead to clinical research into a new form of treatment.
4.Enabling an international clinical trial
Key researchers: Prof Olaf Witt, German Cancer Research Centre, Germany; Dr Darren Hargrave, Great Ormond Street Hospital, UK.
As part of this programme, the researchers will
work with the European Society for Paediatric Oncology to launch a clinical
LOw Grade Glioma In Children
(LOGGIC). LOGGIC is the first trial that will evaluate the impact of low grade
brain tumours and their treatment in children. This trial will assess the child's quality of
life, including visual and neurological function
Low grade brain tumours account for about half of all paediatric brain tumours. Yet they're often neglected in favour of their more malignant counterparts. But the often chronic nature of low grade brain tumours means they can have a lifelong burden for those affected. Symptoms of the tumour, along with the side-effects of treatment, and the constant threat of multiple tumour recurrences over long periods of time, can have a severe, negative effect on quality of life. This must change and Dr Jones's research is helping accelerate progress.
Low grade brain tumours are the most common childhood primary brain tumour. Children with this tumour can go through many rounds of treatment, including surgery, chemotherapy, and radiotherapy. This often has a profound long-term effect on their health and wellbeing.
This research will help these children and their families by finding tailored treatments that could improve their quality of survival, helping us to halve the harm that brain tumours have.
Identification of a previously misdiagnosed subtype of paediatric low-grade tumours using our new analysis tool looking at molecular ‘tags’ on DNA.
The team have been heavily involved with the upcoming update of the World Health Organisation’s global reference guide for the diagnosis and classification of tumours. The update will include the new subtypes of paediatric brain tumours. It aims to improve diagnosis and ensure the best possible treatment options are given to people with brain tumours.
The researchers are continuing to investigate the origin of children’s low grade tumour cells by looking for the brain cells they come from. This information could allow for the generation of better, more precise therapies.
Generating a new cell model of pilocytic astrocytoma (PA), the most common type of paediatric low-grade brain tumour. This new model not only tracks if the drugs are able to kill tumour cells, but it also tells us how the drugs affect the internal processes of the cell. This more detailed information enables us to better compare drugs and see what combinations might work best.
The team are collaborating with several pharmaceutical companies, using the new PA model, to test how effective new individual drug, or drug combinations, are at attacking tumour cells. This could potentially lead to the identification of new and/or improved treatments for PA.
They will also continue to develop models to better reflect the diversity of low-grade tumour types.
The team previously discovered that chemicals released by cells in PA induce a ‘hibernation’ state in nearby tumour cells. Although this has a positive effect in slowing tumour growth, it also makes the tumours resistant to typical chemotherapies. To address this they have explored a brand-new avenue of brain tumour research which uses a class of drugs known as ‘senolytics’. These drugs specifically attack the hibernating tumour cells and have shown early positive results in the laboratory.
Expanding their research on the use of senolytics the researchers hope to begin a clinical trial to test their effectiveness at killing chemotherapy resistant tumour cells soon.
Because of our funding the team have launched the LOGGIC Core (LOw Grade Glioma In Children) clinical study which is testing whether trametinib (a ‘MEK’ inhibitor that targets active signalling molecules in tumour cells) is better at treating low grade gliomas than the currently used chemotherapy. So far, they have recruited over 250 children from across Europe to the first phase of the study. The tumours from these children are currently being screened for the next phase of the trial, which we anticipate will start early in 2021.
Alongside the expansion of the clinical trial, the trial team plan to open a LOGGIC BioClinical Database across the UK and European. This will enable more individuals the opportunity to join the study and help test if the MEK inhibitor trametinib, is a better treatment approach than current standard therapy.
Toby Ritchie was diagnosed with a low grade brain tumour at the age of five. In 2015, his dad – Rob – led a unique and physical demanding challenge – Everest in the Alps – to raise money for The Brain Tumour Charity. The team raised an incredible £3m which has been put towards The Everest Centre.
We are thrilled that the money raised through Everest in the Alps is being used to establish The Everest Centre. This pioneering research will allow scientists to accelerate progress towards finding more effective treatments for the disease and could be revolutionary in improving the lives of children living with low grade tumours.
Your donation could help fund the following equipment Dr Jones uses for his research:
Group leader Dr David Jones will be working closely with researchers in both London and Germany. They aim to make new discoveries about low grade brain tumours and translate them into new clinical treatments