Scientists have found a new way to starve cancerous brain tumour cells of energy in order to prevent further growth.
The findings by Professor Silvia Marino and her team at the Centre of Excellence at Queen Mary University of London, funded by Shenley Wood charity Brain Tumour Research, could see a breakthrough in the way that children with medulloblastoma brain tumours are treated in future.
Medulloblastoma is the most common high-grade brain tumour in children. Some 70 are diagnosed in the UK each year. Survival rate is 70% for those whose tumour has not spread but it is almost always fatal in cases of recurrent tumour.
Ashya King from Milton Keynes was five when he was diagnosed with an aggressive medulloblastoma and underwent surgery in July 2014 to remove the tumour. His parents sparked a manhunt by taking him out of hospital without doctors’ consent to have proton beam therapy (an advanced form of radiotherapy) abroad, then unavailable in the UK. Ashya is now cancer-free, but is profoundly disabled, having developed a condition known as posterior fossa syndrome from his surgery, and faces many future battles. Sadly, his parents have since separated, with dad Brett remaining in Milton Keynes with the couple’s seven children, while mum Naghmeh is living in their holiday home in Spain.
Prof Marino from Queen Mary University of London said: “We have identified a novel way that grade four medulloblastoma is able to adapt its metabolism and grow uncontrollably. Significantly, we have also shown how this energy supply can be blocked. These exciting results bring hope of developing new targeted treatments for patients with this aggressive paediatric brain tumour.”
“Medulloblastoma occurs in four distinct subgroups (WNT, SHH, G3 and G4). Despite our growing knowledge of the molecular differences between these subgroups, current options are surgery together with radiotherapy and/or chemotherapy for all patients. We desperately need to understand the key molecular events driving tumour growth in each subgroup to design new, less toxic, targeted treatments.”
Silvia’s team has previously demonstrated that, alongside high levels of BMI1, G4 medulloblastoma cells also lack a protein called CHD7 (referred to as BMI1High;CHD7Low). This combination of changes, or signature, is thought to contribute to the development of grade four medulloblastoma.
Now the team has shown that high levels of BMI1 enable the cancer cells to adapt their metabolism and grow aggressively. This change can be reversed by treating the cells with inositol hexaphosphate (IP6). The team also showed that when IP6 was combined with chemotherapy – in this case cisplatin – they observed an increased ability to kill the tumour cells.
Hugh Adams, Head of Stakeholder Relations at Brain Tumour Research said: “These very exciting results reveal a new way for epigenetics to control metabolism within tumour cells. Clinical trials are now required to test the ability of combining IP6 with chemotherapy to treat G4 medulloblastoma, offering promise to a particularly vulnerable group of patients.
“It is great news and brings some much-needed hope for the future. There is still some way to go but we hope that a clinical trial could be up and running in as little as two years.
“Brain tumours kill more children and adults under the age of 40 yet, historically, just 1% of the national cancer spend has been allocated to this devastating disease. Brain Tumour Research is determined to change this.”
Peter Gardiner, from Aston Clinton, near Aylesbury, lost his 13-year-old son to medulloblastoma in November 2017. Next month, May, marks six years since his diagnosis.
“I can only describe our experience as a long hell. Firstly, Ollie was diagnosed, then he went through surgery and extensive treatment. When we were told there were no further options for him in the UK, we crowdfunded £500,000 so he could have immunotherapy in Germany. It was our only hope and, sadly, it didn’t work,” he said.
Ollie’s family generously donated £187,000 of the residue of their fundraising to Brain Tumour Research which is funding post-doctoral researcher Sara Badodi who works alongside Prof Marino.
Pete said: “We were overwhelmed by the support of friends, family and strangers who stood by us in our hour of need and came together to help us do the very best we could for our son. It means the world to think that, because of him and the love people showed to us, others might not have to go through what we did.”