Modern medicine has made enormous advances in treating children suffering from leukaemia. Nevertheless, this disease still makes up a third of all children who do not survive cancer. Research in the team’s laboratories is based upon finding new treatments for subtypes of leukaemia that are difficult to treat, through understanding the disease at the molecular level.
Harnessing SMAD7 induced transcriptional pathways for novel anti-leukaemia therapies
Dr Owen Williams
UCL Great Ormond Street Institute of Child Health
1 December 2017
Cancer cells often exhibit an exaggerated dependence upon certain normal cellular signalling pathways. In common with other cancers, leukaemia cells depend on high levels of cellular cholesterol and fatty acids for growth and survival. We have discovered a novel cellular signalling pathway regulated by the molecule SMAD7 in leukaemia cells that ensures cholesterol and fatty acid synthesis. Blocking this pathway leads to elimination of leukaemia, suggesting that this approach may be used in combination with other drugs to enhance leukaemia therapies.
This project will establish whether SMAD7 inhibition can enhance the therapy of childhood leukaemia and identify drugs that are effective at this inhibition. This project opens up the possibility of using existing drugs that target cholesterol in novel leukaemia therapy, as well as identifying clinically relevant drugs that may have unanticipated anti-leukaemia activities. This will improve the treatment options for children with leukaemia who are currently in need of novel therapies, reducing their chemotherapy burden and enhancing therapeutic efficacy.
This project will involve the laboratories of Dr Owen Williams and Dr Jasper de Boer, in the Cancer Section of the UCL Great Ormond Street Institute of Child Health, and those of Professor Olaf Heidenreich and Dr Deepali Pal, Northern Institute for Cancer Research, Newcastle University.
The project will also benefit from collaboration with Dr Philip Ancliff and Dr Sujith Samarasinghe, senior consultant paediatric haematologists at GOSH. The laboratories of Dr Williams, Dr de Boer, Professor Heidenreich and Dr Pal have a track record in childhood leukaemia research. Over the last decade they have developed various models to investigate the molecular basis for leukaemia progression and susceptibilities to novel therapies.
Together with Dr Ancliff, Dr Williams and Dr de Boer have also initiated a drug redeployment initiative in the Cancer theme of the joint institutions to identify and develop novel leukaemia therapies that can be ‘fast-tracked’ into the clinic. Dr Ancliff and Dr Samarasinghe will bring important clinical insights into this project and provide invaluable clinical experience to ensure the timely incorporation of novel therapies into clinical trials and practise.
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