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Review
. 2022 Jun 28:2022:4165808.
doi: 10.1155/2022/4165808. eCollection 2022.

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

Raja Nur Firzanah Syaza Raja Sharin  1 , Jesmine Khan  1 , Mohamad Johari Ibahim  1 , Mudiana Muhamad  1 , Joanne Bowen  2 , Wan Nor I'zzah Wan Mohamad Zain  1
Affiliations
Review

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

Raja Nur Firzanah Syaza Raja Sharin et al. Biomed Res Int. .

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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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Conceptual framework of the underlying mechanisms of lapatinib-induced diarrhoea. Treatment with lapatinib not only inhibits tumour cell survival and proliferation but also inhibits ErbB1 normal function in gastrointestinal mucosa (1). ErbB1 inhibition is hypothesised to disrupt gut homeostasis (2) by triggering excessive leakage of LPS or bacterial antigens into the mucosa, causing upregulation of inflammatory cytokines (3) that progressively destroys the intestinal epithelium, subsequently permitting more antigen leakage, aggravating inflammation responses thus compromising intestinal barrier permeability by altering intracellular TJPs (4 and 5), hence diarrhoea. Abbreviation: LPS: lipopolysaccharide; TJPs: tight junction proteins.
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