Precision medicine for childhood cancer

27 September 2016
Childhood Cancer 2016 word cloud graphic

Our recent conference, Childhood Cancer 2016, provided a forum for scientists and clinicians to discuss advances in the treatment of childhood cancer.

But we may now have reached the limits of what existing treatments can achieve. New and innovative treatments are desperately needed to save the thousands of children worldwide who cannot be cured with existing therapies.Four out of five children diagnosed with cancer can now be cured. This survival rate is double what it was 50 years ago so there is much to celebrate. But increases in survival rates have slowed overall, and particularly in aggressive tumours where conventional treatment has always been a challenge. And still one child in five is dying - either because there is no effective treatment for their particular cancer or because their body cannot withstand the toxic side-effects of standard treatment.

In the main, the gains in survival have not been achieved through the introduction of new drugs but rather through improvements in the way we use existing drugs. We’ve improved diagnostics and learned how to stratify children so that they can be treated under the regime that has been shown to be most effective for their particular situation, using the best combinations of therapy. Improvements in surgical techniques, radiotherapy and supportive care have played an important role.

But we may now have reached the limits of what existing treatments can achieve. New and innovative treatments are desperately needed to save the thousands of children worldwide who cannot be cured with existing therapies.

What is precision medicine?

The relatively recent ability to rapidly and affordably map out the genetic code of any individual person and any cancer they develop holds great promise for the design of targeted treatments for children with cancer, with the aim not only to improve cure rates but to also reduce toxicity. This type of precision medicine has been used successfully in some of the common adult cancers.

Precision medicine approaches involve the use of new treatments to target specific changes in individual patients’ tumour DNA.Precision medicine approaches involve the use of new treatments to target specific changes in individual patients’ tumour DNA. The goal is to individualise treatments according to the genetic characteristics of the patient’s cancer. This approach is in contrast with existing treatment protocols that define tumours mainly according to their location and use toxic drugs to kill cells in a much less targeted, less efficient way.

The case of Allison Schablein, a young brain tumour patient from the US, demonstrates the premise of precision medicine. Allison was four years old when doctors found multiple tumours in her brain and spine. One tumour was removed surgically; the remainder were surgically inaccessible and quickly became resistant to chemotherapy. There seemed to be nothing else that doctors could do for Allison until genomic testing revealed that her tumours had a genetic mutation called BRAF, seen in some cases of the skin cancer melanoma.

Allison was enrolled onto a clinical trial of dabrafenib, a drug targeting the BRAF mutation in (adult) melanoma patients. Within two months, Allison’s tumours were gone or, at least, had shrunk so much they were no longer visible on an MRI scan. Three years on, there are still no visible signs of any tumours.

As with the implementation of any new and highly promising approach, we need to fully understand how the genetics of each tumour predicts which patients will respond most effectively, and in which circumstances.Whilst it might seem odd to treat a skin cancer and a brain tumour with the same drug, this demonstrates the difference in the precision medicine approach, where treatment is based upon common mutations rather than the location of the tumour.

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 as well as the possibility of access to drugs designed to treat adult cancers.

We hope that by matching the best-targeted drugs to patients using the most precise information about their tumours, we will maximise the promise and minimise the toxicity of this new generation of drugs. Of course, treatment is not likely to be universally effective. And, as with any new approach, there will be complications of treatment. Some children will fail to respond and others will develop resistance. As with the implementation of any new and highly promising approach, we need to fully understand how the genetics of each tumour predicts which patients will respond most effectively, and in which circumstances.

Making precision medicine a reality in the UK for young cancer patients

Precision medicine was the focus of the first day of our recent conference, Childhood Cancer 2016. We brought together some of the world’s leading experts in precision medicine and childhood cancer to discuss some of the issues outlined above and to consider the barriers and opportunities for precision therapy for children with cancer in the UK.

Nick Goulden at Childhood Cancer 2016Dr Nick Goulden, Medical Director at Children with Cancer UK, chaired Childhood Cancer 2016. He said:
“There is early evidence that precision medicine works in childhood cancers and can save lives. Crucially for young patients, such targeted therapies could also reduce the burden of toxicity, and help them to improve quality of life both during and after treatment.

However, whilst some colleagues in the US and Europe are already systematically applying this technology to young cancer patients and seeing some success, efforts in the UK have been ad hoc rather than systematically applied in clinical trials.”
photo: Dr Nick Goulden at CC2016

To help drive forward the implementation of precision medicine for young cancer patients in the UK, Children with Cancer UK is supporting the initial phase of a programme to implement DNA sequencing for every child diagnosed with a solid tumour in the UK.

This work is being led by Professor Louis Chesler at The Institute of Cancer Research in London, on behalf of a large multi-centre consortium.Our funding will support the building of a national infrastructure for rapid-turnaround sequencing of tumour DNA from young cancer patients.

Read more: Professor Louis Chesler – Enabling molecular profiling in childhood cancer

A five-point plan for the implementation of precision medicine for children with cancer in the UK

The full implementation of precision medicine for children with cancer requires a huge effort, beyond the means of a single charity, or even multiple charities.

At the same time as providing funding to pump-prime the implementation of DNA sequencing, Children with Cancer UK has launched a five-point plan setting out what needs to happen to ensure that all children diagnosed with cancer in the UK have access to precision medicine by 2020:

  1. Investment in NHS pathology services to ensure that samples suitable for use in precision medicine are available from every child, teenager and young adult with cancer in the UK.
    •    To provide somatic and germ line samples within two weeks of diagnosis or relapse
    •    Initial funding to be led by charities like Children with Cancer UK with a commitment from the NHS to fund as service after proof-of-principle in clinical trials

  2. Development of an Ethical and Governance framework suitable for precision medicine
    •    Department of Health (DoH) to rapidly establish multi-stakeholders group to define ethical guidelines for genetic testing in paediatric cancer, drawing on international expertise
    •    NHS/DoH to develop quality framework for genetic testing including pre- and post-analytic quality assessment

  3. Development of a robust digital infrastructure to support clinical decision-making
    •    Genetic and clinical data to be stored in a secure digital personal medical record
    •    On-going support of a national molecular tumour board of scientists and oncologists that makes treatment recommendations based on personal medical record
    •    Precision cancer medicine in children to be given a central place in the evolution of UK strategy for analysis of big data in healthcare - so that key data from individual digital personal records can be used anonymously to refine the predictive value of testing for future patients

  4. Equality of access to targeted therapies for all patients
    •    Pharma incentivised to make “targeted drugs” known to have potential activity against a molecular lesion found in a patient’s tumour available for children and to work harder to provide child-friendly drug formulations
    •    Regulators and commissioners to accept, facilitate and fund off-label use of targeted drugs in children if recommended by national / international tumour board

  5. Clinical trials to prove the efficacy of precision medicine
    Priority given to development of, and participation of UK in, both small proof-of-concept and large-scale multinational trials of targeted therapies


    “An incredibly important step towards increasing survival…”
    “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, The Institute of Cancer Research
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