Neuroblastoma and Ewing sarcoma research

Providing nearly £4m to establish the children’s cancer research group in Leeds, world-renowned for its research into neuroblastoma and Ewing sarcoma.

Overall, survival rates for children with cancer have improved over the last few decades. But not all young people with cancer have seen the same benefits. Neuroblastoma and Ewing sarcoma are just two examples where the level of improvement has been less than most other cancers. Survival from Ewing sarcoma has not changed for more than 30 years. And about 50% of children with neuroblastoma still have 'high-risk' disease, meaning that these children sadly have a lower chance of survival in the long term.

These cancers have high chances of recurrence and spreading to other parts of the body. Both are driven by cancer cells that are resistant to treatments and can recreate tumours sometimes more than a decade after initial treatment.

Basic research has increased our knowledge of neuroblastoma, Ewing sarcoma, and other childhood cancers. We must use this knowledge to develop new treatments and better tests to meet the needs of patients and their families.

Over 30 years ago, consultants in Leeds saw an opportunity to set up a laboratory which could directly improve the lives of children with cancer. The lab would focus on ‘translational’ research: taking basic research and using it to develop new tests, treatments and practices, making progress quicker and more effective.

Following a hugely successful fundraising campaign, the Candlelighters laboratory was opened in 1992 at St James’ University Hospital in Leeds. From the beginning, the lab has been headed by Professor Sue Burchill, who shares the vision of applying scientific research to improve outcomes for young people with cancer.

Candlelighters provided an initial £1m to establish the lab and since then has contributed a further £2.9m to ensure progress can continue. Today, Sue’s lab is known as the Children’s Cancer Research Group and is world-renowned for its translational research into neuroblastoma and Ewing sarcoma. Her team’s research is helping to predict which treatments will be most effective and develop new kinder drugs to prevent cancers from recurring – to give children and young people with cancer the best chance of survival and quality of life after treatment.

The lab focuses on how cancer cells resist treatments and spread to other parts of the body – the main cause of death from these cancers in children and young people.

Biomarkers are molecules that can be detected and measured in blood or tissue samples. Biomarkers are useful when monitoring cancer and can be used for diagnosis, predicting outcomes for patients, assessing response to treatments, or spotting early signs of relapse.

As part of their research into neuroblastoma, Sue and her team developed a method for detecting cancer cells in the blood, which could indicate that the disease is likely to spread or come back after treatment. Using this test, doctors can identify children who have a very high risk of their disease progressing. The test can also be used to assess the effectiveness of treatment for different patients.

Following Professor Burchill’s work, blood tests like these are now being used in a variety of clinical trials. The hope is that these tests could be used to make early predictions about which treatments would be most effective for a child and monitor in real-time how well that treatment is working.

Sue works with laboratories in 25 countries to standardise methods for the blood test. This will mean that children with neuroblastoma get the same test, no matter where in the world they live. This standardisation makes comparisons across different countries easier, enabling international collaboration and giving more insight.

Identifying biomarkers of cancer recurrence also provides clues to understand what is driving the spread of cancer and relapse in children. In 2017, Candlelighters funded a project led by Sue to investigate what causes neuroblastoma to come back and spread. Through this study, Sue and her team have identified neuroblastoma cells in bone marrow that are resistant to treatments and may be responsible for relapse. They are studying these cells to find weaknesses that could be targeted with drugs.

Developing new drugs to treat children with cancer can take a long time. Identifying and developing a new drug to testing and treating patients with it can take 20 years or more. A much quicker way to get results for young patients is to look at existing drugs and how these can be repurposed with new approaches to treat cancer.

Sue and her team are currently carrying out drug repurposing studies in both Ewing sarcoma and neuroblastoma. The team is looking at more than 1,200 drugs, most of which they already know are safe to use for patients. The team is testing the drugs using state-of-the-art techniques to prioritise the most promising drugs to take forward for validation.

Using existing drugs has the added benefit that a lot is already known about how they work. This means they can be used as research tools to understand biology and how cancer cells multiply and evade current treatments. For example, research by Sue’s team into a drug called fenretinide has led to a greater understanding of Ewing sarcoma and how it avoids normal treatments. This has helped researchers design new drugs and drug combinations that may be more effective in the clinic than fenretinide itself.

The Children’s Cancer Research Group is now an established institution and continues to progress treatment and understanding of childhood cancers. Because childhood cancers are relatively rare, the lab collaborates with international researchers to help tackle big challenges and questions. The group works with and presents at the International Society of Paediatric Oncology (SIOP), contributing to the worldwide childhood cancer community. Another key focus of their collaboration is with patients and families directly, ensuring their research is relevant to the needs of the people childhood cancer affects most.

Through the research group, Sue has also trained and nurtured a new generation of childhood cancer researchers. This is an essential part of the ecosystem of research as it ensures a pipeline of people who can continue to take research forward and ultimately make the progress that is needed.

The laboratory now receives funding from many sources, safeguarding the future of their vital research.