SRC018 Understanding and preventing bowel cancer in cystic fibrosis
An international, multidisciplinary team of researchers led by Professor Stephen Renshaw at Sheffield University, will be investigating a possible role for the cystic fibrosis (CF) protein, CFTR, in causing CF-related bowel cancer.
There is some research to suggest that people with cystic fibrosis (CF) may be more at risk of developing bowel cancer than people of the same age in the general population; this risk may also be higher in people with CF post-transplant. However, this research is limited, and the same results have not been seen in all studies. Cystic fibrosis researchers around the world are seeking more information to understand the risk of people with CF developing bowel cancer.
More information on bowel cancer and CF can be found on this page of our website.
While more evidence about the chances of people with CF developing bowel cancer are being explored, biomedical scientists within this SRC programme are investigating whether or how disruption to the normal workings of the CFTR protein might directly or indirectly lead to the development of cancer.
The development of cancer is the culmination of a number of damaging changes within cells in the bowel. Professor Renshaw and colleagues have identified a link between the faulty CF protein and some of these damaging changes. This link could explain why people with CF may be at a greater risk of developing bowel cancer, and also explain why those who have had organ transplants may be at a particular risk. More research is required to confirm their findings and explore how and whether these changes can be prevented.
Below is a brief outline of the aims of their research:
Aim 1: Identifying bowel cancer triggers in cystic fibrosis
Each step of the process that leads to bowel cancer will be explored in turn, to understand any role of the CF protein. The researchers will use a number of different laboratory models, including state of the art 3D ‘organoids’ derived from human biopsy tissue, zebrafish and mouse models of cystic fibrosis. These models will allow the researchers to understand the normal role of CFTR in these processes, and the consequences of the presence of mutated CFTR in cystic fibrosis.
Aim 2: Evaluating the effectiveness of drugs to reverse CF triggers for bowel cancer
Alongside the research above that aims to confirm the link identified between mutated CFTR and the development of bowel cancer, Professor Renshaw and his team will explore whether a class of existing and well-used drugs could be beneficial in preventing the damaging effects (if any) of the mutated CF protein. They will test the effects of these drugs in lab models of CF related bowel cancer and study their effects in a small group of people with cystic fibrosis. By the end of their four-year study, the researchers hope to be ready to begin a clinical trial of these drugs.
Principal investigator: Professor Stephen Renshaw, University of Sheffield
- Professor Andres Floto, University of Cambridge
- Professor Carl Smythe, University of Sheffield
- Dr Matthias Zilbauer, University of Cambridge
- Professor Robert Cormier, University of Minnesota, USA
- Professor Ludovic Vallier, University of Cambridge
- Dr Audrey Bernut, University of Versailles Saint Quentin, France
- Dr Patricia Scott, University of Minnesota, USA
- Professor Inke Näthke, University of Dundee