Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2.
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.
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Satoshi
S
Tanida
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Tsutomu
T
Mizoshita
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Keiji
K
Ozeki
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Takahito
T
Katano
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Hiromi
H
Kataoka
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Takeshi
T
Kamiya
Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Takahito Katano, Hiromi Kataoka, Takeshi Kamiya, Takashi Joh, Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya city Aichi prefecture, Aichi 467-8601, Japan.
Takashi
T
Joh
D000818:Animals; D017306:Annexin A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015195:Drug Design; D004359:Drug Therapy, Combination; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
C472822:ANXA2 protein, human; D017306:Annexin A2; D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha
Epidermal growth factors; Integrin α4β7; Shedding; Tumor necrosis factor-α