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What did the project achieve?
“We have made new discoveries about the biology of a form of leukaemia, revealing a potential weakness that we hope to target with existing drugs – offering hope to children whose disease returns after treatment,” says Dr Owen Williams of the UCL Great Ormond Street Institute of Child Health.
Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia – over 400 children under 15 are diagnosed in the UK each year.1 Up to one in four of these children will have a form of the disease called TEL-AML1.2 Thankfully, most are cured after treatment – although they may be left with lifelong, sometimes serious, side effects. But sadly, for some children, their disease comes back and has become resistant to treatment.
“We have now uncovered more about the underlying biological mechanisms that help these TEL-AML1 leukaemia cells to survive and grow – identifying one that we may be able to target,” says Dr Williams.
The team then showed in laboratory experiments that blocking this mechanism causes patient leukaemia cells to die – indicating that it could offer an effective treatment strategy.
“We are now analysing the knock-on effects that occur in leukaemia cells after blocking this mechanism, which we hope will lead us towards existing drugs that could be repurposed for treating the disease,” says Dr Williams.
The main advantage of this approach, compared to developing new drugs from scratch, is that effective treatments should get to patients faster.
References:
- Cancer Research UK Statistics: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/leukaemia-all/incidence#heading-One [website accessed 15 January 2020]
- Loh ML et al. Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01. Blood 2006; 107: 4508–4513. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895800/ Website accessed 17 January 2020
This research was completed on
Around 300 children develop a type of cancer called acute lymphoblastic leukaemia (ALL) each year in the UK.1 This cancer is most common in young children who are less than five years old. Most children with ALL are cured. However, treatment has side effects and some children still lose their lives. Dr Owen Williams, of University College London’s Institute of Child Health, is searching for new treatments for children with a common type of ALL in the hope of reducing side effects and saving more children’s lives.
Action Medical Research and Great Ormond Street Hospital Children's Charity are jointly funding this research.
How are children’s lives affected now?
ALL is the most common type of cancer to affect children.2 It’s an aggressive cancer that develops rapidly, so urgent treatment is needed, but with today’s care children with ALL have a high chance of surviving. Treatment usually involves chemotherapy and steroids, but radiotherapy and sometimes a bone marrow transplant can also be needed.
“Although the outlook is normally very good for children with ALL, it remains important to look for ways to improve treatment,” says Dr Williams. “Children have to go through intensive treatment, which typically lasts for years and can cause unpleasant side effects. Sadly, a small number of children with this type of cancer still die.”
“Possible side effects during treatment include nausea, vomiting, tiredness and hair loss,” continues Dr Williams. “Some children also have problems later in life. For example, their growth might be restricted, they may be infertile and their ALL can recur.”
How could this research help?
The researchers are searching for new drug treatments for a type of ALL that’s called TEL-AML1, after the cancer gene that causes it. One in four children with ALL has this.3
“We’ve discovered that the TEL-AML1 cancer gene turns on a particular pathway inside cancer cells that the cells need to survive,” says Dr Williams. “We’re therefore looking for drugs that turn off this pathway and investigating whether they destroy cancer cells in the laboratory.”
“We’re focusing on drugs that are already used to treat other illnesses,” says Dr Williams. “This speeds up the development process, because information on the safety of those drugs is already available.”
“We hope to find a drug that can be used alongside chemotherapy, so the intensity of chemotherapy can be reduced,” continues Dr Williams. “Our ultimate goal is to spare children from some of the side effects of chemotherapy and protect more children from relapses.”
References
1. Macmillan Cancer Support. Acute lymphoblastic leukaemia (ALL) in children. http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Childrenscancers/Typesofchildrenscancers/Acutelymphoblasticleukaemia.aspx Website accessed 24 November 2015.
2. NHS Choices. Acute lymphoblastic leukaemia. http://www.nhs.uk/conditions/leukaemia-acute-lymphoblastic/Pages/Introduction.aspx Website accessed 24 November 2015.
3. Loh ML et al. Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01. Blood 2006; 107: 4508–4513. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895800/ Website accessed 25 November 2015.
| Project Leader | Dr Owen Williams BSc PhD |
| Project Team | Dr Jasper de Boer BSc PhD |
| Project Location | Cancer Section, Institute of Child Health, University College London |
| Project duration | 3 years |
| Date awarded | 22 July 2015 |
| Project start date | 11 April 2016 |
| Project end date | 10 July 2019 |
| Grant amount | £199,465 |
| Grant code | GN2368 |
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