Bronwen J Mayo1,2, Andrea M Stringer3,4, Joanne M Bowen3, Emma H Bateman3, Dorothy M Keefe3. 1. School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. bronwen.mayo@unisa.edu.au. 2. School of Pharmacy and Medical Sciences, Sansom Institute for Health Sciences, University of South Australia, Adelaide, South Australia, Australia. bronwen.mayo@unisa.edu.au. 3. School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. 4. School of Pharmacy and Medical Sciences, Sansom Institute for Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Abstract
PURPOSE: A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention. METHODS: This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action. RESULTS: Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease. CONCLUSION: This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.
PURPOSE: A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention. METHODS: This is a review of current literature on irinotecan-induced mucositis and GLP-2 analogues mechanisms of action. RESULTS: Recent studies have found alterations that appear to be crucial in the development of severe intestinal mucositis, including early apoptosis, alterations in proliferation and cell survival pathways, as well as induction of inflammatory cascades. Several studies have indicated a possible role for glucagon-like peptide-2 analogues in treating this toxicity, due to its proven intestinotrophic, anti-apoptotic and anti-inflammatory effects in other models of gastrointestinal disease. CONCLUSION: This review provides evidence as to why and how this treatment may improve mucositis through the possible molecular crosstalk that may be occurring in models of severe intestinal mucositis.
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