Barrier Function and Tight Junctions in Tyrosine Kinase Inhibitor-Induced Diarrhoea: A Scoping Review.

Abstract

Introduction: Tyrosine Kinase Inhibitors (TKIs) are widely used in modern cancer treatment and have significantly improved outcomes for many patients. However, their use is frequently limited by gastrointestinal side effects, particularly diarrhoea. Although diarrhoea may appear mild in otherwise healthy individuals, it can substantially impair the quality of life of cancer patients and disrupt treatment continuity. In more severe cases, high-grade diarrhoea may lead to dehydration, malabsorption, fatigue and treatment interruption.

Methods: This scoping review systematically synthesised available evidence examining the relationship between TKI exposure, Tight Junction Protein (TJP) alterations and diarrhoeal outcomes. Studies were identified through structured database searches and analysed descriptively according to TKI class, experimental model and reported barrier-targeted interventions.

Results: Eight eligible studies were included.

Discussion: Most evidence derived from preclinical models and demonstrated alterations in key TJPs, particularly ZO-1 and occludin, following exposure to selected TKIs. Irreversible pan-ErbB inhibitors, such as afatinib and pyrotinib, were associated with broader TJP disruption compared with more selective agents. Despite the high incidence of TKI-associated diarrhoea, barrier-targeted therapeutic strategies were reported for only a limited number of agents.

Conclusion: Overall, the available evidence suggests an association between TKI-induced diarrhoea and epithelial barrier disruption involving tight junction proteins, while also revealing important gaps in translational understanding and barrier-targeted therapeutic development.