A team of researchers have found a novel way of starving brain tumour cells of energy in order to prevent further growth.
The pre-clinical research in human tissue samples, human cell lines, and mice has led to a new way to starve cancerous brain tumour cells of the energy they need to grow. This could lead to changes in the way that some children with medulloblastoma are treated in the future if the findings are confirmed in human clinical trials.
The research, published in Nature Communications, has been carried out by scientists from Queen Mary University of London and funded by the charity Brain Tumour Research.
Medulloblastoma is the most common high-grade brain tumour in children, with 70 children being diagnosed each year in the UK. The survival rate is 70% for those whose tumour has not spread, however, the cancer is almost always fatal in cases of recurrent tumour.
The research looks at inositol hexaphosphate (IP6), a naturally occurring compound present in almost all plants and animals. It shows how it inhibits medulloblastoma and can be combined with chemotherapy to kill tumour cells.
Lead researcher Professor Silvia Marino from the Brain Tumour Research Centre of Excellence at Queen Mary University of London said: “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.
“G4 medulloblastoma is the least understood of all subgroups, despite being the most common and associated with poor prognosis. We have identified a novel way that this type of 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.”
The BMI1 protein
The process of epigenetics – whereby specific genes can be switched on and off to control cell growth – can be disrupted in cancer, leading to overproduction of specific proteins that contribute to the development and growth of a tumour.
Such changes can contribute to the development of medulloblastoma, and a protein involved in this process – known as BMI1 – is found in high levels in a broad range of cancers including brain tumours. In medulloblastoma, high levels of it are found in the G4 subgroup, where it sustains tumour growth.
Professor Marino’s team has previously demonstrated that, alongside high levels of BMI1, G4 medulloblastoma cells also lack a protein called CHD7. This combination of changes, or signature, is thought to contribute to the development of G4 medulloblastoma.
Now the team has shown that high levels of BMI1 enable the cancer cells to adapt their metabolism and grow aggressively.
The team say that this change can be reversed by treating the cells with inositol hexaphosphate (IP6) and demonstrated that when IP6 was combined with chemotherapy they observed an increased ability to kill the tumour cells in mice.
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 the near future.
“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.”