Targeted treatments are key to improving outcomes in paediatric cancers, but their success is reliant on scientists and doctors uncovering the complex biology of different types of tumours. To do this, they need to find better ways to detect and characterise cancers in young patients. Here, we speak with Professor Louis Chesler and Dr Sally George at The Institute of Cancer Research, London, who are working on refining and streamlining clinical testing in this field.
Cancer can affect anyone, regardless of age. In the UK alone, thousands of children and young people are diagnosed with cancer each year. Despite their tender age, they often face the same powerful but gruelling treatments as adult patients – therapies that can cause severe fatigue, pain, nausea and many other side effects.
The physical toll treatment may take on the body and the need to spend regular time in hospitals can prevent patients from doing their usual activities, or limit how much they enjoy them.
Many of the young people who survive cancer go on to experience ‘late effects’ of their treatment, which can appear months or even years after they enter remission. Those who are still growing and developing when they undergo treatment may also sustain bodily damage that leads to long-term health problems.
The Institute of Cancer Research (ICR) is at the forefront of research into cancers in children, teenagers and young adults. Our researchers, who are renowned in their fields, are investigating a wide range of these diseases and taking varied approaches to tackle them.
Previous work has already spearheaded new understandings of the causes of some paediatric cancers and underpinned new treatments. Now, in the hope of achieving this in additional cancer types, some of our scientists are focused on developing innovative new tests capable of providing the biological information that is needed to create and deliver targeted treatments, which are likely to be both more effective and kinder.
We are internationally leading in the study of cancers in children, teenagers and young adults. Our researchers play key roles in international research efforts that are transforming how these devastating diseases are treated, as well as pioneering studies of cancer types not studied elsewhere in the UK. Please support us and help us make a difference to the lives of cancer patients and their families everywhere.
Targeted treatments are key to defeating cancer
The focus on finding a single cure for cancer significantly underestimates the challenge researchers face. Cancer is not a single disease but an umbrella term for more than 200 diseases, all of which involve the body’s cells growing uncontrollably and potentially spreading to other areas of the body.
What’s more, the very nature of cancer – which results from the accumulation of random mutations across thousands of genes and continues to evolve over time – means that every case of cancer is unique.
Targeted therapies are much more refined in approach than standard therapies such as chemotherapy and radiotherapy. They are created based on researchers’ extensive understanding of cancer biology and target specific proteins known to influence the growth, division and spread of cancer cells.
By destroying only cancer cells and sparing healthy tissue, targeted treatments typically cause fewer side effects, making them kinder for patients. They are often more effective too, as different treatments can be directed to the individuals most likely to benefit from them based on the biology of their cancer.
The need for new clinical tests
For a patient to reap the benefits of targeted treatments, their care team must get information about their cancer’s unique pattern of biomarkers – naturally occurring biological molecules, genes or other characteristics. Some biomarkers determine whether a particular treatment will be effective.
A tissue biopsy is often considered the most reliable way to get detailed information about a tumour because the samples provide a large amount of DNA, which helps experts determine the specific mutations or other genetic changes driving the cancer.
Unfortunately, because young children typically have small bodies, performing biopsies on them does not provide enough tissue for pathologists. This leaves them unable to discern at a molecular or immune level what makes the tumour grow and become aggressive. There is also a risk of drawing incorrect conclusions if the sample is not fully representative of the whole tumour.
Researchers cannot simply apply the findings from research in adults because teenage and young adult (TYA) and childhood cancers generally have very different types, frequencies and patterns of mutations. Therefore, a different approach is needed.
Liquid biopsies could transform care
Liquid biopsies are similar in principle to tissue biopsies, but as they use fluids from the body, they are much less invasive.
The ICR scientists working on liquid biopsies in childhood and TYA cancers include Professor Louis Chesler, Group Leader of the Paediatric Solid Tumour Biology and Therapeutics Group, and Dr Sally George, Group Leader of the Developmental Oncology Group. Both groups are working on understanding, identifying and treating neuroblastoma – a cancer that develops in nerve tissue and typically affects children under the age of five.
Professor Chesler’s research also includes medulloblastoma, a form of paediatric brain cancer that is particularly common in children aged between three and nine.
Liquid biopsies are an innovative laboratory test that could identify cancer cells before a tumour forms, transforming diagnosis and treatment and bringing new hope for patients.
Find out more about how liquid biopsies work
Gathering the necessary molecular data
The ICR’s research into liquid biopsies builds on earlier work in paediatric cancer genetics.
Scientists led by Professor Chesler and Dr George recently shared the findings of a UK-based precision medicine study called Stratified Medicine Paediatrics (SMPaeds).
The study showed that tests on blood samples from cancer patients may be superior to standard tissue biopsies in providing information on how a tumour develops over time. The samples contain circulating tumour DNA (ctDNA) – fragments of DNA that dying tumour cells release into the bloodstream.
Using ctDNA analysis, the team was able, in some patients, to detect DNA mutations that were not revealed by the tissue sequencing. The scientists also compared samples taken from the same patients at diagnosis and relapse, which allowed them to identify genetic changes associated with the return of the disease. They are currently working on translating this work into a standard of care test that could be provided by the NHS.
However, the study also uncovered a significant challenge. Many patients with brain cancer had low ctDNA levels, so analysing blood samples did not provide enough useful information.
Undeterred, the researchers are working on alternative solutions.
New biomarkers
The team is looking to create tests that work on other biological markers, which are more likely to be present at sufficiently high levels for analysis.
The scientists are investigating the feasibility of looking for a type of DNA molecule called extra-chromosomal circular DNA (ecDNA), which originates from chromosomes but exists separately to them. ecDNA has been detected in tissue samples from multiple types of paediatric tumours, including neuroblastoma, glioblastoma and medulloblastoma. They are also trialling the use of innovative technology that makes it possible to isolate and characterise whole cancer cells shed by brain tumours into the blood.
In the longer term, these approaches could promote earlier diagnosis and inform the development of effective new treatments.
New techniques
The researchers are also planning to assess additional blood-based testing platforms that could prove transformative for treatment. These capitalise on new technology that is much quicker than current processes, requires less DNA and may detect additional genetic changes associated with the development of childhood cancer.
In addition, they are evaluating a test that uses a lateral flow format, similar to the tests used during the Covid-19 pandemic. It has been designed to support the early detection of cancer relapse and can be analysed directly in the clinic. The hope is that early detection of relapse will allow children and young people to join clinical trials when they have a very low level of disease that may be more responsive to treatment.
“Our goal is to ensure that no child or young adult will be treated on a clinical trial without real-time, detailed molecular testing,” said Dr George. “The ability to monitor treatment in this way will maximise the chance of clinical trials extending patient survival or even curing the cancer in certain tumour types.”
Strong partnerships lead to change
The ICR is privileged to have many extremely talented scientists dedicated to childhood and TYA cancers. They, in turn, are honoured to be working with some inspiring family charity partners, without whose support they would not be able to do what they do.
Dr George spoke of her gratitude for our family charity partners. She said:
“Their vision is for every child diagnosed with cancer to survive, reach adulthood and enjoy a good quality of life. To turn that vision into reality, they have chosen to support ground-breaking paediatric cancer research programmes here at the ICR.
“Having been through something no parent should endure, it is my firm opinion that they are well placed to explain to us what is needed in the clinic that might improve children’s lives, and in that regard, they have done so. They have measurably contributed to our work in so many ways.”
A charity that has long supported the ICR’s liquid biopsy work is Abbie’s Fund, which was set up the year before Abbie Shaw died of neuroblastoma aged just five. Diagnosed before her second birthday, Abbie “squeezed absolutely every opportunity out of every minute she had”, but she spent much of her life undergoing various invasive tests and treatments for her recurrent cancer. This inspired Abbie’s Fund to fundraise in support of research that could spare other children from having to endure so many procedures.
Another charity funding this research is Aoife’s Bubble's, which was set up by Eilish Flanagan after her three-year-old daughter Aoife passed away from germ cell cancer – a childhood tumour that usually develops in the ovaries or testes. It usually responds very well to chemotherapy, but Aoife survived for just five days following her diagnosis. Eilish believes that if healthcare professionals had detected the disease when Aoife first presented with stomach pain, the outcome would have been very different.
Wanting to give other families “the chance to make as many memories as possible”, Eilish has chosen to support research that will offer children a quick and accurate diagnosis and help clinicians track treatment response over time so that they can adapt the protocol if necessary.
The ICR’s important work is also generously supported by Christopher’s Smile, a charity set up by Kevin and Karen Capel in memory of their son, Christopher, who died from medulloblastoma shortly before his sixth birthday. Christopher’s Smile has worked with the ICR for more than a decade, during which it has raised more than £1.2 million for our research into paediatric cancers.
Kevin and Karen have also actively campaigned for changes to European legislation that would remove existing restrictions preventing children from accessing the latest scientific technologies. In recognition of their outstanding support for paediatric cancer research and their leadership in influencing childhood cancer treatment policy, Kevin and Karen Capel were awarded Honorary Degrees of Doctor of Science (Med) in 2019.
The dedication of our family charity partners, set up when a family has been touched by cancer, drives forward our research immeasurably. We are so grateful to work with such passionate organisations and receive their generous support.
Learn more about our charity partners
Looking ahead
With consistent support and generosity from family charity partners, and through collaboration with The Royal Marsden NHS Foundation Trust, the ICR has already made pioneering advances in the development of cancer tests for children.
And despite the complexities of paediatric cancers, researchers are increasingly optimistic about the future of care. The move towards using drugs that attack individual cancer-causing proteins and genes looks set to prove transformative for many patients.
Professor Chesler credits the families he works with as playing a significant part in advancing cancer research. He said:
“Often, the smartest person in the room is not the doctor or scientist. Our family charity partners have challenged us, taught us and led us to solutions that we hadn’t conceived of ourselves. At times, they are already looking farther over the horizon than we are, and this pushes us to stretch our goals beyond what we thought was possible.
“I am privileged in my career to have come across people with such clarity of vision and dedication of purpose.”