Children's Brain Tumour Research Centre

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Research highlights 2019

Franziska Linke
Click on the boxes below for recent research highlights 
 

 

Ependymoma

Brain cancer metabolism describes all the chemical reactions required by cancer cells to survive, grow and invade the brain. There is an urgent need to better understand the metabolism of childhood ependymoma, in order to target and kill ependymoma cells completely. Currently, up to half of children with ependymoma relapse, and at this stage, the cancer is very resistant to chemotherapy.

Funding from the Stoneygate Children’s Brain Tumour Research Fund has allowed Dr Ruman Rahman and team to develop a new method to examine cancer metabolism in childhood ependymoma. This method allows for both metabolites, and RNA (a molecule which is essential to key cell functions including coding and expression of genes) to be extracted from the same cells. The study presents a first-in-kind description of the childhood ependymoma metabolome and reveals that the ‘posterior fossa A’ and ‘supratentorial RELA fusion’ patient sub-groups are metabolically distinct brain tumours. Future plans, are to study differences within distinct regions of tumours, and find out more about how proteins are used by the cancer cells to metabolise. This knowledge could help develop future therapies to stop the tumour cells surviving and growing.  

Cancer metabolism research at CBTRC has been strengthened further through the appointment of Dr Madhu Dandapani in April 2019, as Clinical Associate Professor. Dr Dandapani has recently been awarded a grant by the Little Princess Trust to develop her work in this area, focussing on ependymoma and paediatric high grade gliomas.

 

Cannabidiol 

There is a lot of interest in the potential of Cannibidiol (CBD) as a therapy for brain tumours. Brain Tumour Action, The Astro Brain Tumour Fund, and fundraising led by Mr Steve Frost have jointly funded research exploring how paediatric brain tumour cells react with CBD.

We have been studying the impact of different concentrations of CBD on 3D tumour cell models and also in conditions without oxygen (as this best mimics the conditions of the tumour in the brain). The research has focussed on ependymoma and paediatric high grade glioma cells. We have found that the cells do die, but there appears to be a cascade of events which lead to the cell death after a single CBD dose and we need to find out more about this.

Some patients currently take cannabis oil as adjuvant therapy for a brain tumour. We plan to replicate how they do this (e.g. 3 days on, 3 days off) in the laboratory, so we can understand its impact on the tumour cells.

Future work in this area may see us strengthen work with other researchers, including those at the University of Western Australia, to explore the effects of CBD on immune reactions.

Finally, we intend to combine our CBD work with our previous study into the Ketogenic diet, to see if the two therapies interact with each other by looking at cells cultured in the absence of glucose and dosed with CBD. It would also be interesting to see if there is any increase in cell death if the cells are exposed to radiotherapy, as radiotherapy causes cellular damage which may enable more damage to be caused to the cell by the ketogenic diet or CBD or both.

 
 

Glioblastoma

Dr Ruman Rahman and Dr Stuart Smith have previously evaluated the unique clinical potential of a biodegradable polymer called PLGA/PEG, to act as a delivery system for chemotherapy drugs. The polymer forms a paste when mixed with water, which can be applied to the brain cancer cavity created after removal of the bulk tumour during surgery. The paste then releases chemotherapy drugs into the brain, thereby targeting the remaining cancer cells which cannot be safely removed by surgery and which cause the cancer to return.

Thanks to funding from The Sam White Legacy, Rahman & Smith in partnership with John Hopkins University (USA) have now shown a significant survival benefit in animals with brain tumours, when olaparib is delivered during neurosurgery using PLGA/PEG. This effect was further enhanced when combined with radiotherapy. The findings are exciting as olaparib has already been clinically-approved for treating ovarian cancer patients. This study supports the consideration of olaparib to be repurposed for brain tumours.

A manuscript is being prepared for submission to the international journal Science Translational Medicine.

 

Medulloblastoma

Medulloblastoma is the most common aggressive brain tumour of childhood and accounts for a quarter of all brain tumours. Many medulloblastomas are metastatic at diagnosis i.e. cancer cells have already spread away from the original tumour. Spread of cancer cells or, even worse, evidence of additional tumours growing away from the original site, makes it less likely that current therapies will be successful. The majority of these patients will die despite intensive treatment.

Dr Beth Coyle and her team are developing develop new model systems that mimic human tumour behaviour in order to investigate what causes tumour spread. Their research focusses on discovering more about medulloblastoma cells, and how they behave. Knowing more about how their behaviour and how this can be identified, could lead to further studies by the scientific community to develop new treatments, and therapies.

Current projects include testing novel drugs which could inhibit medulloblastoma cells from migrating, and identifying markers of metastasis in Cerebrospinal Fluid (CSF) using imaging machines.  The group have also found that medulloblastoma tumours manipulate their microenvironment to support specific patterns of migration. Further work is being conducted to understand the underlying mechanisms.

We are anticipating a number of published papers on our work in 2019/20, including in Neuro Oncology, BMC Biology and the European Journal of Nuclear Medicine and Imaging. 

 
 

 

HeadSmart

HeadSmart Clinical Oncology Education Fellow, Dr Shaarna Shanmugavadivel, was awarded a prestigious NIHR Fellowship which commenced in January 2019. This Fellowship takes forward the model developed by HeadSmart and will examine national diagnostic intervals and referral pathways for childhood cancer to develop gold standard evidence based guidelines for clinicians. 

The team are developing a new section of the Headsmart website, with training for health professionals, to help them identify patients with brain tumours.

 

Clinical Trials

We now have 100 patients that have consented to be part of the research study, Biomeca, which is part of the SIOP Ependymoma II Clinical Trial (see Molecular Neuro-Oncology Page). 

We are in discussion with the NHS about setting up a national Multi Disciplinary Team meeting for all paediatric brain tumours (similar to the Ependymoma Management Advisory Team, which CBTRC leads). Were this to be established, this will ensure the Clinicians are provided with support for complex cases, and alongside this, it would advocate for and encourage best practice in sample collection. This would mean scientists will have the opportunity to have the best access to samples from which they can find new diagnostic methods, treatments and cures for childhood brain cancers.