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Childhood brain tumours: breakthrough could speed new treatments

A breakthrough by researchers could benefit young patients undergoing novel treatments for life-threatening brain tumours. 

A team from The Institute of Cancer Research, London, has developed a non-invasive imaging technique which could be used to monitor more accurately the effects of a new generation of brain tumour drugs on children, potentially speeding up clinical trials and accelerating progress towards better survival rates. 

The findings, published today (Friday) in the scientific journal PLOS ONE, focus on genetically-tailored treatments for one of the most difficult-to-treat types of childhood brain tumour – glioblastoma. Children with a glioblastoma survive for just over a year on average. 

The research, by a team from the ICR and The Royal Marsden NHS Foundation Trust, was funded by The Brain Tumour Charity. It centred on a specific cancer cell signalling pathway in the brain, the phosphoinositide 3-kinase or PI3K pathway. 

PI3K has been shown to play a key role in the development of glioblastoma as well as in drug resistance. It  hampers the effect of temozolomide, the standard chemotherapy drug which is used in conjunction with surgery and radiotherapy to treat this type of tumour. 

Blocking the PI3K pathway has been at the forefront of recent research into more effective treatments for glioblastoma. 

Clinical trials of molecular agents that inhibit this pathway are already under way in adults with glioblastoma, and there are plans to begin similar trials for children in the future. 

Working on paediatric glioblastoma cells in the laboratory, the ICR team found a way to assess the impact of drugs on the PI3K pathway without the need for recurrent tumour sampling requiring surgery or a conventional scan involving radiation. 

They used two PI3K inhibitors discovered at the ICR, in collaboration with company Piramed Pharma, one of which is currently undergoing clinical trials. 

Using an imaging technique known as magnetic resonance spectroscopy (MRS), they discovered that the inhibitors reduced the levels of two key “metabolites” – the biochemical markers that result from cell activity – controlled by the PI3K pathway. 

This reduction in levels of the two metabolites, called phosphocholine and lactate, may provide a clinical imaging tool to measure whether these new agents are working to block the PI3K pathway. 

The study was part of a wider ICR programme to improve the testing of promising new treatments for children, with the aim of introducing PI3K inhibitors to future early stage clinical trials at The Royal Marsden and other hospitals. 

The researchers, led by Professor Martin Leach, conclude that these metabolite changes have “considerable potential as non-invasive biomarkers of drug efficacy”. 

Professor Martin Leach, professor in physics as applied to medicine at The Institute of Cancer Research, London, said: “The prognosis for children with glioblastoma is devastatingly poor. 

“We need to find out whether the new genetically-tailored treatments that we believe to be the way forward are as effective as we would like them to be. 

“Based on this promising work in cells, we hope to develop a straightforward, radiation-free magnetic resonance spectroscopy (MRS) scan that will help us to assess the impact the treatment is having and potentially accelerate progress in future trials towards improving survival rates. 

“We could use the test results to work out how individual patients are responding to treatment, helping us select the most appropriate treatment.” 

Sarah Lindsell, chief executive of The Brain Tumour Charity, said: “When a child is diagnosed with a brain tumour, part of the agony for every family is the prospect of high-risk surgery. 

“But families are also understandably desperate to be involved in clinical trials – and to access cutting-edge treatments - if there is the smallest chance it could help their child. 

“A test which measures the effectiveness of a brain tumour treatment without the need for repeated biopsies  - or exposure to radiation - would make a significant difference. 

“This breakthrough shows that the research we fund is having a real impact on children and families affected by brain tumours.”

Dr Lynley Marshall, consultant in paediatric and adolescent oncology drug development at The Royal Marsden Hospital and one of the researchers and co-authors on the paper, said:  "The results of this preclinical study are promising. 

“They provide further motivation for us to translate non-invasive biomarker techniques such as this into the clinical setting quickly, to incorporate them into future clinical trials of new molecularly-targeted anti-cancer drugs and to help optimise treatment for our young patients with poor-prognosis tumours." 

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