Leukaemia – reversing drug resistance if the cancer comes back | Children's Charity

Leukaemia – reversing drug resistance if the cancer comes back

Project LeaderDr F W van Delft, MD PhD FRCPCH
Project team
  • Dr A Krippner-Heidenreich PhD
  • Professor J A E Irving PhD
  • Dr C Halsey BMBCh FRCPath PhD
LocationNorthern Institute for Cancer Research, Wolfson Childhood Cancer Research Centre, Newcastle University
Other locations
  • Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow
Duration3 years
Grant awarded30 July 2018
Provisional start date1 November 2018
Provisional end date31 October 2021
Grant amount£208,120.00
Grant codeGN2709

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Background

Acute lymphoblastic leukaemia is a type of blood cancer that usually develops quickly over days or weeks. It is the most common cancer in children and young people with around 500 new cases diagnosed each year in the UK in people aged 19 years or younger. Almost a third of cases occur in children aged 4 years or younger. Between 70 and 100 of these children are diagnosed with a disease subtype called T-cell acute lymphoblastic leukaemia (T-ALL). Although the majority of young patients with T-ALL are cured with chemotherapy, sadly in around 20 per cent, the cancer eventually comes back (relapsed childhood T-ALL) and is then almost impossible to cure with currently available treatment, including bone marrow transplantation, as the leukaemia has become drug resistant. These researchers have identified a gene which plays an important role in the growth and survival of T-ALL cells. In laboratory studies, they found that blocking this gene with two drugs already used to treat acute lymphoblastic leukaemia, caused the T-ALL cells to die and reversed drug resistance.

The research project

In order to confirm their initial findings that these two drugs given together kill T-ALL cells, the researchers now plan to test their effects in a mouse model of human T-ALL. They will compare the effects of placebo treatment with those of the two drugs given either separately or in combination, on the growth and survival of human cancer cells in the mouse model. After treatment, the team will look at the number of leukaemia cells in the animals' bone marrow, blood, spleen and brain. They expect to find that combined drug treatment leads to the lowest number of leukaemia cells. The researchers will also examine the leukaemia cells in detail looking for biomarkers that predict how they will respond to drug treatment, and mechanisms explaining the combined effect of the drugs in the cells. If they are able to demonstrate the efficacy of their new approach, the team will propose that these drugs should be included in the treatment of relapsed childhood T-ALL to improve the outcome of these children for whom no other treatments exist. 
 

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