Current treatments for childhood acute lymphoblastic leukaemia (ALL) are highly toxic. In this project Professor Enver and his team hope to identify drugs that target specific vulnerabilities of leukaemia cells and combine them together to effectively eradicate the leukaemia cells without harming normal cells.
Targeting RUNX/Core Binding Factor-dependency in relapsed and poor prognosis acute lymphoblastic leukaemia
Professor Tariq Enver
UCL Cancer Institute
London, WC1E 6BT
1 July 2017
Acute lymphoblastic leukaemia (ALL) is the most common type of childhood cancer. While ALL has relatively high survival rates compared to other cancers, children can experience significant short and long-term side effects caused by the therapy they receive. These side effects are explained by the fact that whilst chemotherapy is very effective at killing leukaemia cells it also impacts normal cells. Unfortunately, a lot of children relapse with the disease and they are harder to treat. There is therefore a clear unmet need for less toxic and more effective treatments for childhood ALL. The solution lies in the development of targeted therapies which affect only the leukaemia cells.
In this project Professor Enver and his team have identified a gene called RUNX1, part of the core binding factor (CBF) complex, which may hold the key to targeted therapy in ALL. It has been found that disrupting RUNX1 activity using a small molecule kills leukaemic cells, while sparing normal ones. This unique vulnerability of ALL cells may therefore be exploited to develop a less toxic, targeted treatment for children with this disease.
The funding provided by Children with Cancer UK will allow the research team to better understand how RUNX1 inactivation impacts the expression of other genes in the leukaemic cell. Once these changes have been defined, they can be targeted using highly specific drugs, alone or in combination with RUNX1. The hope is that a combinatorial treatment, eradicting exclusively leukaemic cells, will bring us a step closer to a truly targeted therapy.
Although the prognosis is now very good for children with ALL, current treatments remain highly toxic and involve high levels of chemotherapy. In addition to the severe side effects that children experience during treatment, they may also suffer long term side effects that impose a high burden on the kids, their families and on society. Ultimately, this project aims to develop more targeted and less toxic therapies for childhood ALL by identifying drugs which target vulnerabilities specific to leukaemic cells, thereby reducing the toxic effects of chemotherapy on the rest of the body.
Professor Tariq Enver is a Professor of Stem Cell Biology and a UCL Cancer Institute Director. He is also the Cancer Lead for UCLP AHSC and Lead of the CRUK City of London Centre. He is a world leader in the field of leukaemia and will provide key mentorship and intellectual input on this project.
Dr Elitza Deltcheva is a Research Fellow at University College London.