Read about some of the research we have funded recently
Investigations into EVI1 mediated epigenetic modulation in childhood leukaemia
Dr Stefan Meyer, University of Manchester
Funded by CCLG through The Toti Worboys Fund
High expression of a cancer gene called EVI1 is associated with high risk and poor outcome in childhood leukaemia.
While this cancer gene has been known to be important in myeloid leukaemia for a while, an important role also in lymphoblastic leukaemia has been recently recognised. How EVI1 maintains leukaemia cell resistance during treatment is not fully understood. Building on the team's previous work in myeloid leukaemia, this project grant will fund a PhD studentship to study the effect of this cancer gene on lymphoid mouse blood cells and human leukaemia cells.
The research will be using advanced and novel technology to identify its interaction with other proteins and identify the genes that EVI1 regulates in order to find new ways to treat high risk and poor prognosis leukaemia.
In vitro modelling of MYCN-driven poor prognosis Wilms' tumour for assessment of novel therapies
Dr Karim Malik, University of Bristol
Jointly funded by Bethany's Wish and CCLG
Many cancers occur because they contain excessive growth-promoting proteins, or 'oncoproteins'. Thus, it may be possible to effectively treat cancers with drugs that eliminate oncoproteins.
Wilms’ tumour is a childhood kidney cancer that can be fatal. This study proposes that growth of Wilms’ tumours may depend on the MYCN oncoprotein, and that pharmacologically eliminating MYCN may represent a novel therapeutic avenue for the deadliest form of Wilms’ tumour.
The primary aims of this project are therefore to use existing cell-line models, together with a new human MYCN-driven Wilms tumour model which the team will create, to understand the biological influence of MYCN in kidney and Wilms’ tumour cells, and evaluate drugs that target MYCN dependence in Wilms’ tumour leading to growth inhibition and cytotoxicity.
The techniques used in this study will include immunohistochemistry, human stem cell reprogramming, transcriptomics and proteomics, and high-throughput drug testing. Dr Malik believes that these studies will validate the application of novel therapeutics for the treatment of poor prognosis Wilms’ tumour patients.
Circulating molecular biomarkers for earlier identification of high risk Wilms tumour
Prof Kathy Pritchard-Jones, UCL Great Ormond Street Institute of Child Health and Dr Matthew Murray, University of Cambridge
Jointly funded by Bethany's Wish, CCLG and the Little Princess Trust
Wilms tumour is the commonest kidney cancer in children, with around 80 new cases in the UK each year. For almost 9 in 10 children it is now curable but despite intensive treatment, some children relapse, meaning their cancer returns. Many relapses come from a group with tumour cells that look “anaplastic” or “blastemal” down a microscope, also known as high risk tumours. The remainder of relapses do not have these features and we currently cannot predict these cases.
The aim of this study is to find ‘biomarkers’ that can identify the high risk tumours early on, as well as children who are likely to relapse. These could then be used to decide adjustments to treatment, monitor how well treatment is working and monitor for relapse. The team's priority is to find a ‘signature’, or ‘fingerprint’ of the tumour that can be detected from a simple blood test. This is to avoid the risks of performing a biopsy in small children. Also, as a biopsy only looks at a tiny section of the whole tumour, it rarely captures all relevant information.
We know that tumours release their damaged (‘mutated’) genetic code (DNA) into the bloodstream, as well as other short pieces of genetic code called microRNAs. New methods are able to detect these tiny quantities of tumour DNA and microRNA directly, and potentially tell us a lot about the composition of the tumour. The team will be applying these methods to tumours and to blood from the same patients. They will focus on time points before surgical removal of the tumour (to see how early we can identify high risk tumours) and afterwards (to check for relapse).
Monitoring microRNA and circulating tumour DNA, with reference to the known mutations in the tumour itself, could allow docotors to keep track of how treatment is working, give early indications of tumours with a high risk of recurrence, and directly detect if the tumour has returned.