A new study has shown the power of genetic testing to pick out the best drugs for children with cancer to extend and improve their lives but only 7% of those with targetable mutations were able to access the appropriate adult drug.

The pilot including more than 200 children found that half had gene mutations that are targetable by adult cancer drugs that are either available as standard treatment or via clinical trials - signalling a new era of precision medicine for young patients.

Although few children on the study went on to receive adult drugs, those who did receive targeted therapies had significant benefits.

The study was led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and offered genetic testing of tumours to children as part of a clinical trial. Some 20 additional hospitals around the UK participated by sending children’s biopsies in for testing.

The research is published in the European Journal of Cancer and was primarily funded by the parent-led charity Christopher’s Smile and the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research (ICR).

Researchers used a gene panel test to read the DNA sequence of 91 genes that drive cancer’s growth and spread from 223 children’s tumour biopsies – looking for potentially ‘targetable’ mutations.

Solid tumours – such as those of the brain, central nervous system, bone and muscle – are rare but have much worse survival rates than children’s blood cancers such as leukaemia. Surgery is often not possible and treatment is limited to ‘blunt instrument’ chemotherapies.

The researchers first validated the panel test, showing it to be than more than 99% sensitive at picking up the 91 mutations, even with just 50 nanograms of DNA – which is around 1,000 times less than the weight of a grain of table salt.

Potentially treatable mutations with adult cancer drugs

Using the test, they found 51% of tumour samples tested had mutations that could be targeted by adult cancer drugs.

The most common potentially treatable mutations were in the genes ATRX, CDKN2A and CTNNB1 which were each found in 12 children’s tumours. MYCN mutations were found in 11 tumours and PI3K3CA mutations in 10 tumours.

Three children had BRAF gene mutations – which are common in melanoma skin cancers and can be treated using a combination of the drugs dabrafenib and trametinib.

Using these melanoma drugs, one of the children had their brain tumour held in check for 13 months before developing resistance. Another was on the drug for nine months with no progression of disease. The third child couldn’t tolerate the combination but had a response to dabrafenib for 15 months.

Since the majority of children with targetable mutations didn’t receive adult drugs – because there was no trial available for the drug in children, they were unable to access the drug on the NHS or they were too ill to receive an experimental treatment by the time they were tested.

For eight of the patients, there were samples available at diagnosis and after treatment – and in six of those, testing revealed that the cancer had acquired new mutations as it evolved in response to treatment. That highlights the need to take an additional biopsy at relapse to search for targetable mutations.

For 12 of the children, the researchers were also able to test for cancer gene mutations in DNA released from tumours into the bloodstream from a blood sample. They found blood tests picked up almost all of the mutations found in the tumour, and in some cases they also found extra mutations which were not detected in the tumour region biopsied.

Children deserve the very best cancer treatments

In future work the researchers will use serial blood tests to monitor how tumours evolve in response to therapies – which will be particularly useful in hard-to-biopsy tumours.

Additionally, for children with brain tumours, the researchers are now looking at using samples of cerebral-spinal fluid to find drug targets. Although lumbar punctures are invasive, they are less so than a brain biopsy.

Study author Dr Sally George, Clinical Research Fellow at the ICR and Consultant Paediatric Oncologist at The Royal Marsden, said: “Children deserve the very best cancer treatments, so they can live as long as possible and as well as possible. We desperately need better, more intelligently designed treatments which can give children longer with their families with fewer side effects.

“By testing tumours for specific gene mutations, we have shown it’s possible to identify new smarter, kinder treatment options for children, which may potentially give these patients much longer with their families after conventional therapies have failed.

“But our study also exposes the desperately frustrating barriers that children still face in receiving new treatments – barriers which lie in the regulations controlling how drugs for children are developed and approved.”