Our Funded Research
Kidney Research Projects
Developing a blood test to help identify high-risk Wilms tumours
With Professor Kathy Pritchard-Jones
Wilms tumour is the commonest kidney cancer in children. Most children can be treated successfully, but some children’s cancer comes back after treatment. Wilms tumours that come back often look different through a microscope than those that don’t relapse, but sometimes there’s no way for doctors to predict the possibility of relapse when the child was diagnosed.
Professor Kathy Pritchard-Jones and Dr Mathew Murray are trying to find a genetic ‘signature’ of these high-risk tumours. They will be looking at tiny pieces of DNA and genetic material that have been shed by the tumour to see if there are any that consistently show up in blood tests when a child has relapsed Wilms tumour. They hope that this will help develop a blood test that will catch high-risk cases sooner.
Project title: Circulating molecular biomarkers for earlier identification of high risk Wilms tumour
Lead investigator: Professor Kathy Pritchard-Jones, UCL Great Ormond Street Institute of Child Health and Dr Matthew Murray, University of Cambridge
Funded by: Jointly funded by Bethany's Wish, CCLG and The Little Princess Trust
Funded: November 2016
Award: £84,998.00
Understanding the genetic changes that lead to Wilms tumour
With Dr Sam Behjati
Wilms tumour is a kidney cancer that mostly affects toddlers. It is caused by multiple changes to a child’s genetic code (called mutations), but researchers don’t know which mutations are the most important. Knowing this could help target treatments to create new treatment options for children whose treatment didn’t work, but also to create treatments with fewer short- and long-term side effects.
Dr Sam Behjati and his team at the Wellcome Trust Sanger Institute plan to look at whole genome sequencing data (which contain a child’s entire genetic code) to find out what order the mutations happen in. This will help them understand how Wilms tumours develop and which mutations are key to the cancer’s formation.
Project title: Ordering of driver mutations in bilateral Wilms’ tumour
Lead investigator: Dr Sam Behjati, Wellcome Trust Sanger Institute
Funded by: The Little Princess Trust
Funded: July 2017
Award: £83,844.00
Investigating a newly discovered gene to improve our understanding of Wilms tumour
With Dr Keith Brown
Wilms' tumour is a common childhood kidney cancer that can normally be treated successfully. However, some children’s cancer comes back. It is difficult to predict which children will relapse and it is difficult to cure them. This means that there is still a pressing need to find new methods for predicting which children will relapse and for treating them.
Dr Keith Brown at the University of Bristol has found a gene that is ‘turned off’ in many Wilms tumours. The gene is important to normal kidney growth and development, and when it is turned off it can open the door for Wilms tumours. Keith’s team plan to learn more about the gene, such as how it can lead to Wilms tumours and whether turning the gene back on could be a good treatment for the cancer.
Project title: Epigenetic deregulation of splicing in childhood renal malignancies
Lead investigator: Dr Keith Brown, University of Bristol
Funded by: The Little Princess Trust
Funded: July 2017
Award: £99,465.00
‘Getting it right first time’ for children with renal tumours
With Dr Tanzina Chowdhury
Most children with renal tumours can be successfully treated with surgery, chemotherapy and radiotherapy, but these don’t work for all patients. To improve treatment and quality of life for these children, we urgently need to improve diagnosis and treatment to ‘get it right first time’.
With this project, Dr Tanzina Chowdhury at Great Ormond Street Hospital will try to improve diagnosis and show the best treatments for different children. The research team will review scans and tumour samples to suggest ways to speed up diagnosis and detect high-risk types of renal tumours sooner. They will also evaluate different treatment routes, including delays and outcomes, to find out how doctors can choose the right treatment for the tumour the first time, rather than multiple rounds of harmful medicines.
Project title: Improving prediction of relapse, treatment delivery and outcomes for children with renal tumours in the UK
Lead investigator: Dr Tanzina Chowdhury, Great Ormond Street Hospital
Funded by: The Little Princess Trust
Funded: January 2019
Award: £97,504.06
A new way of treating Wilms’ tumour
With Dr Karim Malik
Wilms’ tumour is the most common type of childhood kidney cancer. Some children’s cancer comes back after their treatment - this can be difficult to find treatment options for.
Dr Karim Malik and his team at the University of Bristol are looking into oncoproteins – tiny proteins inside cells that promote cancer activity. They believe that medicines removing these oncoproteins could effectively treat cancers. The team have identified an oncoprotein that already has medicines that would work against it. They plan to see whether this medicine has an effect on Wilms’ tumour cells, and to understand how the oncoprotein affects the cancer’s progression.
Project title: Targeting gain of function p53 in poor prognosis Wilms' tumour via histone methyltransferase inhibition
Lead investigator: Dr Karim Malik, University of Bristol
Funded by: The Little Princess Trust
Funded: August 2019
Award: £106,266.50
The Little Princess Trust Knowledge Bank of Wilms Tumour
With Dr Sam Behjati and Professor Kathy Pritchard-Jones
Wilms tumour is the most common type of kidney cancer for children. One of the challenges treating Wilms tumour is knowing who needs intensive treatment and who doesn’t need chemotherapy alongside their surgery.
Dr Sam Behjati and Professor Kathy Pritchard-Jones are building a ‘Knowledge Bank’ that combines information about the genetics of a child’s tumour with the results of the child’s treatment. They hope to find genetic markers that would give doctors an idea of whether their patient’s Wilms tumour is aggressive and needs intensive treatment alongside surgery to remove the tumour. The team also hope that their data will help to improve the treatment of children with Wilms tumours by tailoring treatment intensity to individual children, based on the predictors they have found.
Project title: The Little Princess Trust Knowledge Bank of Wilms Tumour
Lead investigator: Dr Sam Behjati (Wellcome Sanger Institute) and Professor Kathy Pritchard-Jones (University College London)
Funded by: The Little Princess Trust
Funded: December 2019
Award: £1,492,047
Assessing a potent combination treatment to fight Wilms tumour
With Professor Karim Malik
Wilms tumour, a type of childhood kidney cancer, happens because the cells contain too many growth-promoting proteins. In Wilms’ tumour, the cancer depends mostly on a protein called MYCN. Reducing the amount of MYCN in cancer cells could be a way to treat Wilms tumour. However, it is hard to target MYCN directly.
Professor Karim Malik’s lab at the University of Bristol has found a way to attack it in other cancers by combining medicines which target another protein that MYCN relies on, called PRMT5. Not only could this form a new treatment for high-risk Wilms tumour, but it could also be safer and more effective due to it being a combination treatment where each drug is given at a lower dose.
In this project, Professor Malik will use cancer cells grown from patient samples and other models of Wilms tumour to understand how proteins like PRMT5 work in Wilms tumours, what they do, and how medicines targeting them can fight cancer.
Project title: A potent synergistic and selective combination methyltransferase therapy for poor prognosis Wilms' tumour
Lead investigator: Prof Karim Malik, University of Bristol
Funded by: The Little Princess Trust
Funded: July 2023
Award: £229,004.10
Understanding how Wilms tumour cells escape chemotherapy
With Dr Bettina Wilm
Researchers believe that a key reason why Wilms tumours come back after treatment is because some cancer cells are not killed during treatment. One of the ways cancer cells survive is by becoming inactive, but these inactive cells can later re-activate and cause the cancer to grow back and spread elsewhere in the body. Researchers believe this is because any surviving cancer cells communicate with nearby inactive cells following the end of chemotherapy.
Dr Bettina Wilm, at the University of Liverpool, wants to understand more about these processes, from communication and re-activation of cancer cells to how different types of cells behave. In this project, Dr Wilm will be studying cancer samples from Wilms tumour patients, looking at their behaviour, genetics, what molecules are present in the cell and how they interact with other cells. This project could help doctors identify which Wilms tumours are potentially more likely to grow back and could also identify targets for new treatments that would help prevent this.
Project title: Molecular characterisation of cancer stem cells and their microenvironment in Wilms tumour in the quest for new cancer treatment strategies in high risk patients
Lead investigator: Dr Bettina Wilm, University of Liverpool
Funded by: The Little Princess Trust
Funded: July 2023
Award: £170,787.77
Making Wilms tumour cells go green
With Mr Max Pachl
Wilms tumour is a type of kidney cancer that sometimes grows back after treatment. The best way to prevent this is by using a combination of treatments, including surgery to remove the tumour. However, it is difficult for surgeons to know where the cancer ends and healthy tissue starts. This means they may leave cancer cells behind that can lead to the cancer growing back.
Mr Max Pachl at the University of Birmingham is working on a new dye that could make Wilms tumour surgery easier, better, and safer. In this project, he will be testing how effective the new dye is on 3D clumps of Wilms tumour cells, and comparing it to other dyes. The dye could be used in surgeries to make cancer cells glow green.
This means that surgeons can see exactly which areas are cancer and which are healthy. This means they can remove as much tumour as possible and mark areas for targeted radiotherapy. This may lead to lower relapse rates and treatment related complications.
Project title: Near Infra-red fluorescence in Wilms tumour organoids.
Lead investigator: Mr Max Pachl, University of Birmingham
Funded by: The Little Princess Trust
Funded: February 2024
Award: £186,617.65
Understanding how lymphatic vessels talk to childhood kidney cancers
With Professor David Long
Many children and young people with kidney cancers are diagnosed too late. This means that the cancer has already spread, making it harder to treat. Some of the exciting new treatments for other cancer types don’t work for kidney cancer. We need to understand more about how kidney tumours grow and spread, so that all children can get effective and safe treatments.
Professor David Long works at UCL Great Ormond Street Institute of Child Health. His lab has found that there are lots of lymphatic vessels in kidney tumours. These specialised tubes are part of the lymphatic system and transport cells, molecules, and waste out of tumours. However, they can also communicate with cancer cells. In this project, Professor Long will look at this communication.
He wants to find out how the vessels communicate with cancer cells, and whether these messages are different in higher risk tumours. He hopes find messages between lymphatic vessels and cancer that could predict the outcome of a child's kidney cancer.
Project title: Investigating the interaction between lymphatic vasculature and the tumour microenvironment in childhood kidney cancer and its prognostic implications
Lead investigator: Professor David Long, UCL Great Ormond Street Institute of Child Health
Funded by: The Little Princess Trust
Funded: February 2024
Award: £241,169.48
UMBRELLA plus – working towards molecular-driven treatments for children with kidney cancer
With Dr Tanzina Chowdhury
Wilms tumour is a type of childhood kidney cancer that can be treated with surgery, chemotherapy, or radiotherapy. Whilst this works for most children, there are still improvements needed to Wilms tumour care. In this project, Dr Tanzina Chowdhury at Great Ormond Street Hospital has a two-pronged approach to improving care.
The first is to improve genetic testing by offering NHS whole genome sequencing to all children with kidney cancer in the UK. Her team will analyse the data created to understand more about how kidney cancer responds to treatment, improve the accuracy of diagnosis, and identify targets for treatment. Secondly, Dr Chowdhury will look at whether special blood tests can support diagnosis and monitoring.
She hopes these tests could diagnose children faster and detect relapses sooner. Together, these aims will improve outcomes for all children with kidney cancer, including Wilms tumour.
Project title: UMBRELLA plus: A study designed for the implementation, evaluation, and development of molecular-driven treatment in children with renal tumours
Lead investigator: Dr Tanzina Chowdhury, Great Ormond Street Hospital
Funded by: The Little Princess Trust
Funded: February 2024
Award: £829,526.75
