Understanding the evolution of Barrett’s oesophagus
Dr Stuart McDonald in our Centre for Tumour Biology will receive a programme foundation award of ~ £1.2 million from Cancer Research UK. This funding will allow the group to study how the pre-cancerous condition Barrett’s oesophagus evolves into cancer through investigating changes in the tissue over time; both clonal (genetic) and architectural (its physical structure).
With this award the team hopes to determine how Barrett’s evolves into cancer and find novel biomarkers that can change how we look after patients with Barrett’s oesopahgus.
While Barrett’s is common in the UK at ~2 per cent of the population, an individual’s risk of developing cancer is low, 0.3 per cent of all cases progress, and unfortunately we currently have no way of predicting who will develop cancer or not.
This means all patients with Barrett’s are subjected to regular, invasive endoscopic surveillance to detect cancer every few years regardless of actual cancer risk. Our researchers hope to help change this.
Predicting cancer risk in Barrett’s
Barrett’s oesophagus is a premalignant disease that is characterised by metaplasia (a change from one tissue type to another) that involves the replacement of the normal lining of the oesophagus with one that is similar to that of the stomach or intestine.
The current view is that this is due exposure of the oesophagus to chronic acid/bile reflux that results in repeated ulceration and repair by neighbouring stomach tissue.
Patients with oesophageal cancer have a very poor survival rate and this is in part due to a lack of understanding of the evolution of the precancer conditions such as Barrett’s oesophagus. Dr McDonald said:
Endoscopic surveillance is very expensive and is a particularly unpleasant experience for the patient. If 99.7% of patients are not at risk then we have to find new biomarkers for cancer risk to stratify surveillance to only those that are at risk of developing cancer and identifying them before they develop any signs of cancer. We can only do this by understanding the true nature of glandular evolution within the Barrett’s lesion.
They have previously shown that the architecture of Barrett’s resembles the stomach lining and that it can further develop characteristics of the intestine on the cellular level. Barrett’s is a glandular condition and earlier projects have found a range of gland types each with their own cellular makeup.
Dr McDonald has developed an innovative approach where tissue architecture and genotype are analysed together to provide an effective means of measuring evolution in Barrett’s and therefore a more effective cancer risk stratification. Data obtained from this study will form the framework for developing evolutionary biomarkers as a model for cancer risk.
We do not understand how the Barrett’s gland phenotype evolves and the aim is to develop a tool whereby a pathologist can assess cancer risk through histological analysis of routine tissue sections.
The research plan covers three main aims
- Understanding how different Barrett’s gland types are clonally related to each other.
- Assessing gland diversity along with genetic diversity over time in at-risk patients.
- Investigating future cancer risk of patients already diagnosed and endoscopically treated for the early signs of cancer.
With thanks to Dr Stuart McDonald