Identification of cancer stem cell markers in paediatric glioblastomas

15 September 2015
Professor Martin Leach, The Institute of Cancer Research, London

Paediatric glioblastoma is a devastating brain tumour that few young patients survive. The poor outcome has been attributed in part to the presence of a population of cancer stem cells that are resistant to treatment. Professor Leach and colleagues will study the properties of these stem cells to aid the development of new treatment approaches.

Amount of grant: £235,854 | Date of award: May 2015

Overview

Paediatric glioblastoma (pGBM) is an aggressive brain tumour that fewer than one in five young patients survive.

Despite recent improvements in our knowledge of the biology and genetics of pGBM, along with advances in surgery, radiotherapy and chemotherapy, the outcome for children with these tumours remains poor. It is one of the few childhood cancers where there has been no improvement in survival over the last 30 years.

The poor outcome in pGBM has been associated with the presence of a small population of cancer cells called cancer stem cells (CSCs). These cells have been recognised as a potential cause of tumour growth, cell production, drug resistance and metastasis.

Research in this field has had little success to date, partly due to continuous diversification of CSCs within the tumour; this makes them difficult to detect and characterise. For this reason, it would be of considerable value to identify specific features of CSCs that would enable scientists to design treatments to target them.

Because of their location in the brain, pGBMs are typically inaccessible and hard to biopsy, meaning that the only way to detect and characterise tumour regrowth and treatment resistance at an early stage is by imaging. Specialist imaging techniques such as magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) scanning are powerful tools used to non-invasively assess the metabolism of cancer cells, useful for characterising disease and assessing response to therapy.

In this project, Professor Leach and colleagues will use non-invasive imaging techniques to characterise the differences between CSCs and the non-stem cancer cells. They aim to identify specific metabolic features of CSCs that can be used to aid the design of new therapies.

About the research team

The team is excellent and this is the major strength of the proposal. What I particularly like is the combination of expertise in cell biology and genetics with imaging in both MR and PET.
External reviewer
The lead investigator, Professor Martin Leach, is responsible for long-standing programmes of research developing and applying magnetic resonance techniques to identify and monitor important processes in cancer, particularly in relation to new cancer therapies.

His colleagues, Dr Chris Jones and Dr Gabriela Kramer-Marek, contribute valuable expertise in the genetics of childhood brain tumours and molecular imaging respectively.

Most of the day-to-day work on the project will be carried out by Dr Alice Agliano, who has an excellent track record in the field and extensive experience in cancer biology, metabolism and imaging technology.

The Institute of Cancer Research (ICR) provides the ideal environment in which to carry out this work. At the beginning of 2015, a new £20m dedicated pre-clinical Centre for Cancer Imaging (CCI) opened at ICR, providing state-of-the-art facilities and a highly collaborative working environment for multidisciplinary teams of cancer researchers.

What difference will this project make?

Overall, this is an excellent proposal from a world-leading group.
External reviewer
Research into childhood brain tumours is highly challenging and, whilst understanding of the biology of GBM in adults has increased over many years, GBM in children has remained an under-investigated disease. The outcome for young patients remains poor and there are numerous barriers to our understanding of the best treatment strategies.

It is clear that better understanding of the role and characterisation of cancer stem cells is needed in order to develop therapies that directly target these cells, overcoming problems with treatment resistance.

This project therefore has the potential to contribute to the development of new drugs for pGBM, improving the outlook for children with this devastating tumour.

Read more: Our brain tumour initiative | Patient story: Aidan

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