Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review

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2022

Authors

Raja Sharin, R.N.F.S.
Khan, J.
Ibahim, M.J.
Muhamad, M.
Bowen, J.
Wan Mohamad Zain, W.N.I.

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Chupradit, S.

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Journal article

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BioMed Research International, 2022; 2022(1):4165808-1-4165808-13

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Raja Nur Firzanah Syaza Raja Sharin, Jesmine Khan, Mohamad Johari Ibahim, Mudiana Muhamad, Joanne Bowen, and Wan Nor I'zzah Wan Mohamad Zain

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Abstract

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.

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© 2022 Raja Nur Firzanah Syaza Raja Sharin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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