Enabling molecular profiling in childhood cancer

29 September 2016

Professor Louis Chesler, The Institute of Cancer Research

Detailed analysis of the genetic characteristics of a child’s tumour can give important additional information about the tumour and how best to treat it. This is called precision medicine. This project aims to put in place the necessary infrastructure to introduce the systematic testing of newly diagnosed and relapsed patients.

Amount of grant: £125,666 | Date of award: July 2016

Professor Louis CheslerOverview

Around 1,600 children are diagnosed with cancer each year in the UK; around 80 percent of these children can be cured using existing treatment approaches.

However 250 children die from cancer every year in the UK. Many more are left with an impaired quality of life as a result of treatment-related harm.

The need for targeted treatment (precision medicine)

Outcomes vary within, as well as between, different tumour types. Doctors need to be able to find out as early as possible who is likely to do well and which treatment would be best.

Cancer is caused by damage (mutations) to the DNA of cells. The pattern of mutations varies between tumours that have historically been grouped together. The ‘mutation profile’ of a tumour may be more important when treating the cancer than the location of the tumour; detailed DNA analysis (‘sequencing’) can therefore give important additional information about a child’s tumour and how best to treat it. This is called precision medicine.

The arrival of a new generation of targeted ‘precision’ cancer drugs that attack tumours with specific genetic mutations opens up the possibility of new, more targeted treatments for young cancer patients. This may improve the success of treatment and reduce the risk of side effects.

The need for molecular diagnostics (patient stratification)

To correctly determine which treatment would be best for a child with cancer, doctors must have rapid access to the results of a detailed analysis of the tumour DNA. This information must then be considered by a panel of experts on a ‘molecular tumour board’ who will recommend the best treatment option.

Whilst this approach is in progress in the US and some parts of Europe, it has not been implemented in the UK in any systematic way because of a lack of investment in the necessary infrastructure. This project will now begin to put in place that infrastructure in order to make precision medicine a reality for young patients in the UK.

As the first stage of a project known as Stratified Medicine Paediatrics 1 (‘SMPaeds 1’), tumour samples will be sent to either the local pathology team or the central children’s cancer biobank in Newcastle. Tumour DNA will be extracted and sent to a specialist laboratory at the Royal Marsden Hospital, London where a technique called Next Generation Sequencing will be used to look for a range of alterations in specific regions of DNA known to be often damaged in cancer.

The results of this analysis will be linked to the patient’s clinical information and discussed by a molecular tumour board comprising specialists from around the country and, on occasions, abroad. The Board will look at the results and discuss the best treatment for a patient.

Project scope

Children with Cancer UK has provided 12 month funding to begin to roll out SMPaeds nationally, pending the agreement of a larger multi-year grant involving other funding partners. Our initial funding will enable the project team to build national infrastructure to deliver clinically actionable genomic data to treating clinicians.

During this initial 12 month phase, the team expect to sequence 4-500 samples from newly diagnosed and relapsed patients and report the information back to treating clinicians for use in treatment plans.

Results from the analysis of a child’s tumour will need to be available within four weeks to be of value in their treatment. The patients most likely to benefit from precision medicine are those who have already relapsed on standard treatment and the condition of these patients may well deteriorate quickly. Time is therefore of the essence in obtaining results that can be used to dictate the use of a new drug. By looking at the details of the sample collection, processing and analysis it will be possible to reduce the time taken to obtain results and allow patients to be entered into trials using targeted therapy.

About the research team

This work is being led by Professor Louis Chesler, Professor of Paediatric Cancer Biology at The Institute of Cancer Research (London) and Consultant Paediatric Oncologist at the Royal Marsden Hospital. However, there is a large consortium involved in the implementation of SMPaeds, combining clinical and basic scientists, oncologists and pathologists at many centres. The members of the team have extensive links to groups throughout the UK and abroad, access to state-of-the-art clinical and research facilities, and an excellent track record in research.

What difference will this project make?

New approaches are urgently needed to improve the outcome of children with hard-to-treat and relapsed solid tumours and to minimise the side effects of drugs already in use.

In order to take advantage of the arrival of a new generation of ‘precision’ cancer drugs that target specific genetic mutations, we urgently need to implement DNA sequencing for all young cancer patients.

“Application of modern technologies to treatment is very important because it maximises the chance that this new generation of ‘targeted’ cancer drugs can be most effective, by matching patients to the best drug using the most precise genetic information about their tumour. A more comprehensive and structured approach to genetic testing to match children with cancer to specific targeted treatments could be an incredibly important step towards increasing survival.”
Professor Louis Chesler

This project represents an important step forward in providing access to precision medicine for young cancer patients in the UK. It will begin to build the national infrastructure to move paediatric tumour tissue from the point-of-care to sequencing facilities for rapid-turnaround diagnostics and to deliver genomic data back to the treating clinicians in support of personalised cancer medicine.

During the tenure of this short project, some 4-500 children will have access to DNA sequencing, with results fed back to their doctors to inform their treatment.


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