Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review
Lapatinib, an orally administered small-molecule tyrosine kinase inhibitor (SM-TKI), is an effective treatment for ErbB2-positive breast cancer. However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly...
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| description | Lapatinib, an orally administered small-molecule tyrosine kinase inhibitor (SM-TKI), is an effective treatment for ErbB2-positive breast cancer. However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient’s quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. Insight regarding the involvement of ErbB1 in the pathophysiological changes such as inflammation and intestinal permeability as the underlying cause of diarrhoea is covered in this article. |
| doi_str_mv | 10.1155/2022/4165808 |
| format | Article |
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However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient’s quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. Insight regarding the involvement of ErbB1 in the pathophysiological changes such as inflammation and intestinal permeability as the underlying cause of diarrhoea is covered in this article.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2022/4165808</identifier><identifier>PMID: 35800225</identifier><language>eng</language><publisher>New York: Hindawi</publisher><subject>Apoptosis ; Binding sites ; Breast cancer ; Cancer therapies ; Causes of ; Chemotherapy ; Cytokines ; Dehydration ; Development and progression ; Diarrhea ; Digestive system ; Enzyme inhibitors ; Epidermal growth factor ; Epithelium ; ErbB-1 protein ; ErbB-2 protein ; Gastrointestinal tract ; Genetic aspects ; Growth factors ; Health aspects ; Homeostasis ; Inflammation ; Inflammatory bowel disease ; Inhibitor drugs ; Kinases ; Ligands ; Malabsorption ; Oral administration ; Permeability ; Phosphotransferases ; Protein-tyrosine kinase ; Proteins ; Quality of life ; Review ; Targeted cancer therapy ; Toxicity ; Tumor necrosis factor-TNF ; Tyrosine ; Wound healing</subject><ispartof>BioMed research international, 2022, Vol.2022 (1)</ispartof><rights>Copyright © 2022 Raja Nur Firzanah Syaza Raja Sharin et al.</rights><rights>COPYRIGHT 2022 John Wiley & Sons, Inc.</rights><rights>Copyright © 2022 Raja Nur Firzanah Syaza Raja Sharin et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2022 Raja Nur Firzanah Syaza Raja Sharin et al. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-8efdd2b70769cc3773cee537423cb42f5de67885f83059e40eafaaeb0c9a3f8f3</citedby><cites>FETCH-LOGICAL-c453t-8efdd2b70769cc3773cee537423cb42f5de67885f83059e40eafaaeb0c9a3f8f3</cites><orcidid>0000-0002-0054-3684 ; 0000-0002-0420-2780 ; 0000-0003-0876-0031 ; 0000-0003-3826-7360 ; 0000-0002-4761-2472 ; 0000-0001-7929-685X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256418/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256418/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids></links><search><contributor>Chupradit, Supat</contributor><contributor>Supat Chupradit</contributor><creatorcontrib>Raja Sharin, Raja Nur Firzanah Syaza</creatorcontrib><creatorcontrib>Khan, Jesmine</creatorcontrib><creatorcontrib>Ibahim, Mohamad Johari</creatorcontrib><creatorcontrib>Muhamad, Mudiana</creatorcontrib><creatorcontrib>Bowen, Joanne</creatorcontrib><creatorcontrib>Wan Mohamad Zain, Wan Nor I’zzah</creatorcontrib><title>Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review</title><title>BioMed research international</title><description>Lapatinib, an orally administered small-molecule tyrosine kinase inhibitor (SM-TKI), is an effective treatment for ErbB2-positive breast cancer. However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient’s quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. Insight regarding the involvement of ErbB1 in the pathophysiological changes such as inflammation and intestinal permeability as the underlying cause of diarrhoea is covered in this article.</description><subject>Apoptosis</subject><subject>Binding sites</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Causes of</subject><subject>Chemotherapy</subject><subject>Cytokines</subject><subject>Dehydration</subject><subject>Development and progression</subject><subject>Diarrhea</subject><subject>Digestive system</subject><subject>Enzyme inhibitors</subject><subject>Epidermal growth factor</subject><subject>Epithelium</subject><subject>ErbB-1 protein</subject><subject>ErbB-2 protein</subject><subject>Gastrointestinal tract</subject><subject>Genetic aspects</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Inhibitor 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However, its efficacy as one of the targeted cancer therapies has been hampered by several adverse effects, especially gastrointestinal toxicity, commonly manifested as diarrhoea. Although it can be generally tolerated, diarrhoea is reported as the most common and most impactful on a patient’s quality of life and associated with treatment interruption. Severe diarrhoea can result in malabsorption, leading to dehydration, fatigue, and even death. ErbB1 is an epidermal growth factor profoundly expressed in normal gut epithelium while lapatinib is a dual ErbB1/ErbB2 tyrosine kinase inhibitor. Thus, ErbB1 inhibition by lapatinib may affect gut homeostasis leading to diarrhoea. Nevertheless, the underlying mechanisms remain unclear. This review article provides evidence of the possible mechanisms of lapatinib-induced diarrhoea that may be related to/or modulated by ErbB1. 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| subjects | Apoptosis Binding sites Breast cancer Cancer therapies Causes of Chemotherapy Cytokines Dehydration Development and progression Diarrhea Digestive system Enzyme inhibitors Epidermal growth factor Epithelium ErbB-1 protein ErbB-2 protein Gastrointestinal tract Genetic aspects Growth factors Health aspects Homeostasis Inflammation Inflammatory bowel disease Inhibitor drugs Kinases Ligands Malabsorption Oral administration Permeability Phosphotransferases Protein-tyrosine kinase Proteins Quality of life Review Targeted cancer therapy Toxicity Tumor necrosis factor-TNF Tyrosine Wound healing |
| title | Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review |
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