Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

World J Gastroenterol. 2015 Aug 7;21(29):8776-86. doi: 10.3748/wjg.v21.i29.8776.

Abstract

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.

Keywords: Epidermal growth factors; Integrin α4β7; Shedding; Tumor necrosis factor-α.

Publication types

  • Review

MeSH terms

  • Animals
  • Annexin A2 / antagonists & inhibitors*
  • Annexin A2 / metabolism
  • Anti-Inflammatory Agents / therapeutic use*
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / metabolism
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology
  • Drug Design*
  • Drug Therapy, Combination
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Molecular Targeted Therapy
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • ANXA2 protein, human
  • Annexin A2
  • Anti-Inflammatory Agents
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha