Bile acids and Barrett's oesophagus : the development of a functional siRNA screen to identify novel therapeutic targets

Abstract

The development of oesophageal adenocarcinoma (OAC) occurs in a setting of chronic reflux known as gastro-oesophageal reflux disease (GORD) and with a recognised premalignant lesion, Barrett’s oesophagus (BO). BO is characterised by the replacement of squamous epithelium of the distal oesophagus with a columnar epithelium. The presence of GORD is associated with an increased risk of developing BO which in itself carries a high risk for OAC development. Refluxed bile acids have been implicated in this process which is often referred to as the metaplastic-dysplastic-adenocarcinoma (M-D-A) sequence. OAC is an extremely aggressive cancer with a poor prognosis. Therapeutic options for this disease are limited, especially if diagnosed at the later stages. The main aim of this study was the identification of novel therapeutic strategies for the treatment of OAC through the development and implementation of a high throughput siRNA screening approach.