Cancer, as most of us think of it, is a disease suffered by older people. And to a large extent that's true. Over time, due to a combination of variations in our DNA, influences from the environment and the impact of modern lifestyles, the cells in our body can turn against us.
But children and young people also get cancer, and although relatively rare, its effects can be devastating. Brain cancer is the most common cause of cancer-related death in children and young people under 19 years of age. Compared to other cancers, very little progress has been made in improving treatments and survival.
Jo and Andrew Williams lost their son Lucas after he was diagnosed with a brain tumour in May 2015. They set up the charity Lucas’ Legacy in their son’s name, to fund research into, and raise awareness of, childhood brain tumours. Jo told us:
“We lost Lucas, our beautiful only child, following a short battle with a brain tumour. Before this Lucas had never been ill, or had a day off school. After a roller coaster of desperate hope and extreme despair, Lucas died at home – 11 weeks and one day after first becoming ill, and just four weeks away from his seventh birthday.
“After Lucas died, we were so sad to find out how little is invested in developing treatments for children with brain cancer. The standard treatment regimes that children receive for high-grade brain tumours are brutal, and Lucas went through so much.
“He fought so hard, but he deserved so much more, to have better treatments in his brave and courageous fight against this devastating illness.”
Barriers to overcome
As well as investment, a major reason for the slow progress in developing effective treatments for brain tumour is that relatively little is known about their biology.
Around 500 children each year are diagnosed with brain tumours, but this number pales in comparison to many adult cancers. The smaller numbers means fewer and smaller clinical trials and fewer samples for researchers to study.
The brain is also a difficult area to target with drugs due to difficulty crossing the blood-brain barrier – which protects the brain from harm. Brain tumours are often difficult to biopsy, and families are sometimes understandably reluctant to allow an autopsy to donate tumour tissue after their child has passed away.
So there aren't as many samples to study to understand the biology of the tumours – the genetic changes that drove them and potential weaknesses that can be targeted by drugs.
But we are making progress.
The ICR is an internationally leading research centre in the study of childhood cancers and cancers in children, teenagers and young adults.
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Taking a closer look at the biology
Professor Chris Jones is Professor of Childhood Brain Tumour Biology at the ICR. His team aims to uncover what drives the development of childhood brain tumours and find ways to translate these findings into new treatments.
Recently, Professor Jones conducted the largest ever study of deadly glioma brain tumours, gathering genetic data from 910 cases from 20 previously published analyses and 157 new cases, from children or young adults up to the age of 30.
His team found these tumours are actually 10 different diseases that should each be diagnosed and treated based on their specific genetic faults. Some types should be far more treatable using targeted drugs under development or already on the market.
The work led by Professor Jones could also lead to more accurate diagnostic tests and ensure each child received the treatments with the best chance of success.
Targeted drugs tend to have fewer side effects than the aggressive chemotherapy regimes that are currently standard treatment for children diagnosed with a brain tumour. If children were treated with targeted drugs, the hope is they would be more able to enjoy play time with their friends and family during treatment.
Professor Jones, said: “Our study found that tumours that have historically been lumped together under one diagnosis are in fact comprised of many, remarkably different, diseases.
“Treating cancer based only on what we see down the microscope simply isn’t good enough anymore. We need to start thinking about these as completely different cancers and diagnosing and treating them based on their genetic faults.
“It’s exciting that several types look like they could be clearly treatable using either existing drugs on the market or other treatments under development.”
Learning lessons from clinical trials
Another recent international study led by Professor Jones found that children with incurable brain tumours could have benefitted from a potentially life-extending treatment if genetic testing was used to personalise therapy.
The team analysed the DNA of children taking the adult cancer drug Avastin on a clinical trial that was deemed to have ‘failed’ to show benefit. But the researchers found that many of the children with particular genetic traits had actually responded well to treatment when combined with chemotherapy – some surviving more than a year longer than others on the trial.
In these children, Avastin also appeared to cause immune cells to flood in to help destroy their tumours – raising the possibility that they could be good candidates for future immunotherapy.
The research shows the benefits of testing children for genetic mutations in their tumours to make sure they receive the treatment most likely to work.
Selecting the best treatments
With funding from the charity Christopher’s Smile, Professor Louis Chesler, Professor of Solid Tumour Biology at the ICR and a Consultant paediatric Oncologist at The Royal Marsden, developed a new test to help personalise children’s cancer treatment.
The test works by sequencing 81 different cancer genes in children with solid tumour cancers – such as those of the brain – to look for mutations that doctors might be able to target using new or existing drugs.
The test is currently being piloted in a small study, but the ultimate aim is to open up access to more cancer treatments to these children and offer them the same opportunities for personalised cancer treatment that are increasingly becoming available for adults – to improve survival rates and reduce the level of side-effects.
Karen Capel founded the charity Christopher's Smile, alongside her husband Kevin, after their son Christopher died after developing medulloblastoma in 2008. Karen said:
“When our son died there was no biological information available to doctors about individual children’s tumours. There is an urgent unmet need to provide new treatments for those children diagnosed with the most aggressive and hard to treat cancers.
“This test Professor Chesler and colleagues at the ICR developed is a first for children. We believe gene sequencing is the key ‘foundation stone’ in enabling personalised medicine, and it will help to bring new treatments for children a step closer.”
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Collaboration is crucial
Professor Jones and Professor Chesler’s work has only been made possible because they work with colleagues across the world. Collaborating in this way allowed us to gather enough data on these rare cancers to understand better what makes them so aggressive, and what mutations occur that might make them susceptible to different treatments.
The ICR has recently been involved in setting up a new alliance with the University of Cambridge, the UK government and Cancer Research UK to form the new Children’s Brain Tumour Centre of Excellence, harnessing the ICR’s expertise in childhood brain tumours and world-leaders in cancer drug discovery.
The groups will be looking at discovering new drugs for childhood brain tumours, making use of old drugs, and solving the riddle of how to get drugs across the blood brain barrier – a huge challenge that still hasn’t been resolved in modern medicine.
Professor Paul Workman, the ICR’s Chief Executive, said:
“Collaboration is vital in childhood brain cancer research and we’re excited to be able to work in close partnership with our colleagues at Cambridge.
“At the ICR, we’ve made great strides in our understanding of the biology of the different types of childhood brain tumour and, working together, we hope to translate those discoveries into the new treatments that children so urgently need as quickly as possible.
“A brain tumour diagnosis in children is devastating for families. We really need to get much better at making modern, targeted cancer treatments available for children.
“This also means improving access to genetic testing and changing regulations so more drugs get tested in paediatric clinical trials.”
Accessing new treatments
The ICR has been campaigning for some time now to improve access to new drugs for children with cancer.
While adults are increasingly treated with precision medicines targeted to genetic weaknesses in their tumours, children still often get traditional one-size-fits- all chemotherapy, which can cause serious, and long-lasting, side-effects.
With the help of other charities paediatric oncologists and patient communities, we are pushing for a change in EU regulations to make it easier for children to access more cancer treatments – by replacing waivers that allow companies to trial some drugs only in adults and exempt them from carrying out expensive testing of cancer drugs in patients under the age of 18.
Currently, there are significant delays in new drugs becoming available for children, and some drugs may never be formally licensed for paediatric use.
Abbie’s Army, set up by Amanda and Ray Mifsud, is one of the parent-led charities supporting our call to the European Commission, as well as funding our research.
Amanda and Ray lost their six year old daughter Abbie to a rare case of DIPG brain cancer in 2011. The condition is inoperable and incurable – new treatments are desperately needed.
Together they set up Abbie’s Army in November 2012 so that one day parents of children diagnosed with DIPG will not be told that there is no cure and no hope, as they were.
Amanda said: “It’s heart-breaking to know that there might be treatments out there for children with rare cancers, like Abbie’s, but that they aren’t being trialled because of a loophole.
“The current system is failing children with cancer. On behalf of all the families experiencing what we did, we ask the European officials to act on these recommendations.”
What’s next?
Survival from childhood brain tumours has barely improved in the past 30 years. Our recent research has gone a long way to increase our understanding of the biology of children’s brain tumours and develop tests to help improve their treatment options.
There’s still more we need to understand about childhood brain cancers, but we believe we will begin to see very soon that children with cancer will have equal access to cancer drugs that are currently used in adults and much better targeting of these drugs via genetic testing so that children receive the treatments most likely to work for them, with less side effects so they can enjoy playtime and other activities that every child should be able to enjoy.
With increased charity, government and industry investment into brain tumour research, and stronger national and international collaborations, we believe in the future we will see new types of treatment emerge, leading to longer survival and more cures.
For parents like Amanda and Ray, Karen and Kevin, and Jo and Andrew, this isn’t the end of their battle, it’s just the beginning. Jo added:
“It’s heartening to see people like Professor Jones, Professor Chesler and colleagues at the ICR working hard to understand children’s brain tumours better and to develop personalised treatments for children like Lucas – kinder treatments that will give them a better chance of survival.
“We are still so shocked that this happened to our seemingly healthy six-year-old boy. Lucas was a really kind, funny, clever, sporty boy and the centre of our world. We know that he would have grown up to be something really special. We know that he would have changed the world for the better. We still hope he will.”