Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives
Autor: | Deysi Viviana Tenazoa Wong, Jose Mauricio Mota, Carlos W. S. Wanderley, Fernando Q. Cunha, Ronaldo A. Ribeiro, Roberto C. P. Lima-Júnior, Caio Abner Leite, Marcellus H.L.P. Souza |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Oncology Mucositis Cancer Research medicine.medical_specialty Antimetabolites Antineoplastic medicine.medical_treatment Context (language use) Disease RECEPTORES Toxicology Irinotecan Pathogenesis 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine Humans Pharmacology (medical) Receptors Cytokine Pharmacology Chemotherapy business.industry medicine.disease Antineoplastic Agents Phytogenic Intestinal Diseases 030104 developmental biology Fluorouracil 030220 oncology & carcinogenesis Toxicity Cytokines Camptothecin business medicine.drug |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1432-0843 |
Popis: | Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis. A literature search was performed using the PubMed and MEDLINE databases. No publication time limit was set for article inclusion. Here, we found that clinical management of intestinal mucositis and diarrhea is somewhat ineffective at reducing symptoms, possibly due to a lack of specific targets for modulation. We observed that IL-1β contributes to the apoptosis of enterocytes in mucositis induced by 5-FU. However, 5-FU-related mucositis is far less thoroughly investigated with regard to specific molecular targets when compared to irinotecan-related disease. Several studies have proposed that a correlation exists between the intestinal microbiota, the enterohepatic recirculation of active metabolites of irinotecan, and the establishment of mucositis. However, as reviewed here, this association seems to be controversial. In addition, the pathogenesis of irinotecan-induced mucositis appears to be orchestrated by interleukin-1/Toll-like receptor family members, leading to epithelial cell apoptosis. IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated. |
Databáze: | OpenAIRE |
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