Working with the Institute of Cancer Research
The Institute of Cancer Research: Royal Cancer Hospital
Working with the Jack Mylam Foundation
Childhood Cancer – Diffuse intrinsic pontine glioma
Helping every child have a future without cancer
The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research organisations. The ICR’s mission is to make the discoveries that defeat cancer. With our clinical partner The Royal Marsden Hospital we are engaged in a wide range of research across many cancer types to develop new treatments for cancer patients. These treatments are based on an understanding of the genes that cause the disease and then designing and developing drugs that counteract the effects of the faulty genes.
The focus of children’s cancer research at the ICR is the discovery, development and clinical introduction of molecularly targeted therapeutics into the clinic, this includes for paediatric high grade gliomas. This new generation of cancer drugs is more effective through specific targeting and elimination of cancer-associated proteins. This is unlike conventional chemotherapeutic drugs, which target normal cells as well as cancer cells, and are therefore toxic and less effective. Unlike adult cancer, where this new generation of molecularly targeted cancer drugs are already in clinical use, the vast majority of children are still treated with conventional chemotherapy drugs. Our aim is to change this.
Dr Chris Jones of the ICR leads a team to work specifically on developing new treatments for high-grade gliomas – tumours that arise from brain cells of the glial lineage, which control many vital functions. Within this research programme Dr Jones is aiming to learn more about diffuse intrinsic pontine glioma (DIPG). Currently little is known about this disease and we hope to find genetic faults associated with DIPG to help develop new targeted treatments.
Working with the support of charities such as the Jack Mylam Foundation we aim to carry out genome sequencing to identify novel mutations associated with DIPG. Little is known about the underlying biology of the disease, as its location in the brainstem makes surgery impossible, so there are few samples for study. However, by targeting faulty genes with candidate drugs we can efficiently discover the drugs that are effective for treatment of DIPG. State of the art sequencing equipment and imaging techniques are required to accelerate this process to ensure that new drugs are as effective as possible when they reach clinical trials stage.
Funding is still required for this study, for example it costs £5,000 to sequence samples of DIPG, £12,500 to screen candidate drugs against DIPG models and £30,000 for the genetic profiling of the tumours.
“The goal of our work is to identify genetic changes that are
specific to childhood cancers, which can then be used to
classify tumours, guide therapy choices, assess response
to treatment and develop novel therapies.”
Dr Chris Jones: Team Leader, Paediatric Molecular Pathology
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Childhood Cancer Research: Brain tumours Paediatric
Information for The Jack Mylam Foundation
Chris Jones PhD FRCPath
Research achievements in the field of High Grade Gliomas including Glioblastoma and Diffuse Intrinsic Pontine Glioma (DIPG)
Dr Chris Jones and his team concentrates on scanning the genome of paediatric brain tumours to create a catalogue of all the molecular alterations present. Their aim is to find the genes that are driving the development of these cancers, and those allowing the tumours to become resistant to therapy. His team are particularly interested in looking at mutations in genes for which drugs have already been developed for other diseases, as well as identifying potential new treatment targets. The goal is always to turn laboratory-based hypotheses into real, molecularly based treatments for malignant paediatric gliomas.
Dr Jones’ research focusses on the more aggressive high grade gliomas (HGG); in children these tumours tend to be associated with a poor clinical outcome. This includes research on glioblastomas (glioblastoma multiforme or GBM) and Diffuse Intrinsic Pontine Gliomas (DIPGs).
Glioblastomas are malignant high grade gliomas that usually grow quickly and are invasive. There are currently no drug treatments available for these cancers. DIPGs are high grade gliomas that are universally fatal. They occur in the Pons structure within the brainstem and are exceptionally difficult to treat.
Historically, high grade gliomas are a very under-researched area. However, a critical mass of research is building and the ICR’s Chris Jones is an international leader and driving force in HGG and DIPG research.
HGG tumours in general:
The team at ICR have developed the most detailed picture to date of the genome of these aggressive cancers. As these tumours are rare, Dr Jones has forged collaborations with other international organisations in order to collect samples that cover the spectrum of potential variations, and to conduct the most comprehensive possible analysis. Dr Jones’ work has already revealed some significant genetic differences between the adult and child form of the disease, and has highlighted potential new drug targets.
In a recent landmark publication (March 2013), Dr Jones’ team describe the discovery of a genetic mechanism driving the development of childhood glioblastoma. Drugs targeted at this genetic mechanism have already been
developed for use in other cancer types, and the researchers plan to test these in clinical trials of children within the next two to three years.
The researchers showed that mutation of a histone protein called H3F3A – which acts as a gene scaffold – unleashes a chain of genetic activity that can lead to the development of glioblastomas. Specifically, this mechanism switches on a gene called MYCN which is known to cause cancer.
There are drugs currently in clinical trials for other types of cancer which can block MYCN’s activity, and it is possible these could become effective treatments for glioblastoma, and help extend the lives of the young patients affected.
Study author Dr Chris Jones, leader of the glioma team at The Institute of Cancer Research (ICR), said: "Our research greatly improves our understanding of the genetic origins of childhood glioblastoma, and identifies key targets for drug treatment of the disease. At present, childhood glioblastoma is an almost certain death sentence for those who develop it, but we now have some hope that effective treatments may be on the horizon. We want to start testing out our ideas in clinical trials as soon as we can – within the next two to three years."
DIPG specific research:
Dr Jones is the Chair of the SIOPE HGG/DIPG Biology Group – the International Society of Paediatric Oncology Europe, a position for which he was voted for by his peers.
Development of worldwide collaborations to allow researchers to pool their knowledge and samples. This is important given the relative rarity of these types of cancer.
Dr Jones is the Principal Investigator (genomics) on a North American DIPG collaborative grant.
An increasing number of DIPG publications, an area where few others have yet published.
Of particular note, Dr Jones’ team performed the first study to comprehensively analyse the genomes of DIPG biopsy samples taken at diagnosis. This analysis allowed the researchers to identify key biological / genetic features which distinguish DIPG tumours from other paediatric high grade gliomas. Furthermore, the research uncovered the existence of two distinct subgroups of DIPG, and patients in one of these subgroups were found to have a significantly more aggressive cancer. Being able to classify these tumours by virtue of their different genetic features may be particularly valuable for the development of therapies targeted towards these very features.