The role of anti-LeY antibody in the downregulation of MAPKs/COX-2 pathway in gastric cancer

Faisal Aziz, Yan Qiu

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Monoclonal antibody-based treatments of cancer which serve as magic 'bullets' have been established as one of the most successful therapeutic strategies. A variety of antigens has been investigated as targets for the mAb therapy of gastric cancer, including the carbohydrate type 2 blood group antigen. Lewis Y (LeY) is overexpressed on tumor cells surface either as glycoproteins or glycolipids. LeY is difucosylated oligosaccharide with the chemical structure [Fucα1,2Galβ1→4(Fucα1,3)GlcNAcβ1→R], which is catalyzed by fucosyltransferases, such as FUT1 (α1,2) and FUT4 (α1,3). The role of LeY antigen in cancer treatment and prevention has been extensively studied. Moreover, the cyclooxygenase-2 (COX-2) is an early event protein, highly expressed in H. pylori-related gastric cancer. COX-2 may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. The COX-2 is upregulated in a variety of cancers, including gastric cancer. However, its inhibition may prevent or reverse gastric carcinogenesis. H. pylori mediated alteration of COX-2 through MAPKs pathway is one of the mechanisms that is implicated in gastric cancer. We have found COX-2 and LeY to be correlative sources of specific gastric biomarkers in gastric cancer, which is upregulated in the gastric cancer through MAPKs pathway. In addition, the anti-LeY antibody significantly downregulated the COX-2 expression through MAPKs pathway, helpful to the treatment of gastric cancer. In this review, we summarize the therapeutic effect of anti-LeY antibody, including the crucial role of COX-2 and LeY antigen in gastric cancer and discuss the COX-2 inhibition by anti-LeY antibody through MAPKs pathway.

Original languageEnglish (US)
Pages (from-to)469-476
Number of pages8
JournalCurrent Drug Targets
Volume15
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Keywords

  • COX-2
  • FUTs
  • Gastric cancer
  • H. pylori
  • Lewis Y
  • MAPKs
  • NSAIDs

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