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Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy
Melissa Schmidt1,2, Richard J Hackett3, Ann-Marie Baker1
1Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Nature Reviews. Gastroenterology & Hepatology
|November 3, 2021
Summary
Barrett esophagus, a pre-cancerous condition, shows pre-programmed cancer development years before detection. Understanding its evolutionary dynamics offers new therapeutic and personalized surveillance strategies for esophageal adenocarcinoma (EAC).
Area of Science:
- Evolutionary biology
- Cancer research
- Gastroenterology
Background:
- Cancer develops through evolution with significant intratumoural heterogeneity.
- Barrett esophagus (BE) is a pre-malignant condition for esophageal adenocarcinoma (EAC).
- BE lesions can be pre-programmed for EAC progression years before clinical detection, offering a therapeutic window.
Purpose of the Study:
- To explore mechanisms of clonal expansion and contraction in BE.
- To discuss drivers of BE evolution towards malignancy.
- To propose exploiting evolutionary dynamics for improved diagnostics and therapeutics.
Main Methods:
- Review of existing literature on Barrett esophagus evolution.
- Analysis of genetic, epigenetic, and phenotypic factors.
- Exploration of temporal and spatial clonal dynamics.
Main Results:
- BE exhibits clonal mosaicism driven by expansion and contraction.
- Both intrinsic genotypic and extrinsic environmental factors influence BE progression.
- A significant window for intervention exists before EAC development.
Conclusions:
- Understanding BE evolutionary dynamics is key to preventing EAC.
- Novel therapeutic targets can be identified by studying these dynamics.
- Personalized surveillance and improved prognostic tools are potential outcomes.
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