Dr Keith Brown, University of Bristol

01 December 2012
Understanding a new molecular defect in Wilms' tumour

This project focuses on a defect in a gene associated with Wilms' tumour. The research team aims to determine whether this defect could enable doctors to identify ‘high-risk’ patients who need more aggressive treatment to halt the growth and spread of their tumour and whether correction of the defect could represent a new approach to treatment.

Amount of grant: £49,616  |  Date of award: December 2012

Wilms' tumour is the most common form of kidney cancer in children. It affects around 80 children a year in the UK, predominantly children under the age of five years.

Modern treatments - which include a combination of surgery, chemotherapy and, in advanced cases, radiotherapy - have achieved long-term survival of 85 to 90% but unfortunately some children still relapse and die. It is difficult to predict which children will relapse and difficult to cure them when they do.

With improving survival, efforts to identify which children will relapse or die and why current intensive therapy does sometimes fail, have become increasingly important. In this context, the possibility of being able to target therapies to meet the needs of individual children is a high priority.

Dr Brown and colleagues are looking at the chemical changes that affect the expression of a gene known as ESRP2, a gene which they have previously shown to be inappropriately ‘switched off’ in many Wilms' tumours, especially advanced, aggressive tumours. They want to determine whether the deactivation of ESRP2 could be a marker that will enable doctors to identify ‘high-risk’ patients who need more aggressive treatment and whether reactivation of ESRP2 could represent a new approach to treatment.

About the research team
The project brings together two research groups at the University of Bristol. Dr Keith Brown and Dr Karim Malik run the cancer epigenetics lab and have both published extensively in this field over a number of years. The laboratory of Dr Sebastian Oltean is focused on the factors influencing tumour growth and suppression and has a wealth of experience in the techniques required for this project

What difference will this project make?
Although the survival rate for Wilms' tumour is now 85 to 90%, modern treatments place a heavy burden on young patients and carry a risk of both short- and long-term side effects. Furthermore, a percentage of patients still do not survive; doctors are unable to clearly predict which children face poorer outcomes.

Ultimately, this project could lead to improved survival and improved quality of survival, through better targeting of existing therapy, and also potentially to the development of new therapies.

Read more: Wilms' tumoursTreatments | Long-term and late effects of treatment


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