Why we focus on Oesophageal Cancer
Patients with oesophageal cancer have a poor survival rate (less than 12% of patients survive more than 5 years). There are two major reasons for such a poor prognosis; oesophageal cancers present at an advanced stage and that we do not fully understand the evolution of common precursor conditions such as Barrett’s oesophagus.
Barrett’s is the erosive replacement of the normal squamous epithelium with a metaplastic columnar phenotype and confers a 40-fold increase in oesophageal cancer risk over the normal population. The cancer risk for an individual Barrett’s patient is low but all patients are enrolled in regular and life-long endoscopic surveillance programmes in which there are no predictive biomarkers to evaluate an individual’s risk of developing cancer. When we consider that there are large numbers of Barrett’s patients, predicting an individual’s risk of developing cancer becomes critical.
What we do
- Determine how clones expand within Barrett’s lesions
- Investigate the clonal evolution of Barrett’s glands in the progression to cancer
- Evaluate patterns of genetic and phenotypic diversity in Barrett’s glands as a means to determine cancer risk in patients
- We are affiliated with Prof David Kelsell, Centre for Cell Biology and Cutaneous Research, Blizard Institute who studies the development of dysplasia in oesophageal cancer.
- Timmer, M. R. et al. Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study. Gut (2015) doi:10.1136/gutjnl-2015-309642
- Lavery et al. Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus. Gut. 2015 10.1136/gutjnl-2015-310748
- Martinez et al. Longitudinal single cell clonal analysis reveals evolutionary stasis and predetermined malignant potential in non-dysplastic Barrett's esophagus. Nat Comms. 2016 (In press)
- Lavery et al. The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands. Gut. 2014 Dec;63(12):1854-63
- McDonald et al. Barrett’s oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol 2015;12(1):50-60
- Blaydon et al. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet. 2012 Feb 10;90(2) :340-6
Who does the research
- Cancer Research UK
- Barts and the London Charity
- Medical Research Council