The molecular pathways involved in the development and treatment of oesophageal cancer are complex. Recent large-scale genome sequencing studies have delivered novel insights into aetiology and possible targeted treatments. Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct entities. At the molecular level OSCC is more similar to squamous cell cancers in other organs than OAC. Whilst considerable heterogeneity exists in both tumour types new data suggests that driver gene events and mutational signatures may be able to categorise tumours into potentially actionable subtypes. Taken together these findings not only suggest new avenues for treatments in a cancer type with appalling outcomes, but also a new era of molecular rather than purely anatomical classification and staging of oesophageal cancer.
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