Targeting the Wnt signaling pathway to treat Barrett's esophagus.
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.
Clément
Geneviève
G
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
Jablons
David M
DM
Benhattar
Jean
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D051153:Wnt Proteins