Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy

Cancer development is a dynamic evolutionary process. This Review explores the mechanisms underlying clonal expansion and contraction as well as the evolutionary dynamics in Barrett oesophagus and its progression to dysplasia and oesophageal adenocarcinoma. The implications for patient management (including surveillance, risk stratification and therapy) are also explored. Cancer development is a dynamic evolutionary process characterized by marked intratumoural heterogeneity at the genetic, epigenetic and phenotypic levels. Barrett oesophagus, the pre-malignant condition to oesophageal adenocarcinoma (EAC), is an exemplary system to longitudinally study the evolution of malignancy. Evidence has emerged of Barrett oesophagus lesions pre-programmed for progression to EAC many years before clinical detection, indicating a considerable window for therapeutic intervention. In this Review, we explore the mechanisms underlying clonal expansion and contraction that establish the Barrett oesophagus clonal mosaicism over time and space and discuss intrinsic genotypic and extrinsic environmental drivers that direct the evolutionary trajectory of Barrett oesophagus towards a malignant phenotype. We propose that understanding and exploiting the evolutionary dynamics of Barrett oesophagus will identify novel therapeutic targets, improve prognostic tools and offer the opportunity for personalized surveillance programmes geared to prevent progression to EAC.

Automated summary

Cancer development is a dynamic evolutionary process with intratumoural heterogeneity. Barrett's esophagus serves as a model system to study malignant evolution, with evidence suggesting pre-programmed progression to esophageal adenocarcinoma years before clinical detection. Understanding the evolutionary dynamics of Barrett's esophagus may lead to novel therapeutic targets and personalized surveillance programs to prevent progression to EAC.