Targeting the Wnt signaling pathway to treat Barrett's esophagus

Expert Opin Ther Targets. 2007 Mar;11(3):375-89. doi: 10.1517/14728222.11.3.375.


Barrett's esophagus (BE) is an acquired condition in which the normal squamous epithelium in the distal esophagus is replaced by a metaplastic columnar epithelium, as a complication of chronic gastroesophageal reflux. The clinical significance of this disease is its associated predisposition to esophageal adenocarcinoma (EAC). Recently, and similarly to other human malignancies, the Wnt signaling pathway and its key component beta-catenin have been implicated in the carcinogenesis of BE. Although mutations in adenomatous polyposis coli (APC) or beta-catenin are rare in EAC, alterations of upstream components, such as overexpression of Wnt2 ligand or downregulation of Wnt antagonists may play dominant roles in the activation of the Wnt pathway. Increasing evidence suggests that inhibiting the Wnt pathway may be a new targeted therapy for the treatment of cancers and could, therefore, be promising for the cure of EAC, which remains a highly lethal disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / etiology
  • Adenocarcinoma / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Barrett Esophagus / complications
  • Barrett Esophagus / drug therapy*
  • Barrett Esophagus / metabolism
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / etiology
  • Esophageal Neoplasms / metabolism
  • Humans
  • Wnt Proteins / antagonists & inhibitors*
  • Wnt Proteins / metabolism


  • Antineoplastic Agents
  • Wnt Proteins