Pathophysiological mechanisms underlying diarrhea across generations of EGFR-TKIs: The role of ERBB signaling and potential therapies
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Issued Date
2025-11-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-105016306153
Journal Title
Biomedicine and Pharmacotherapy
Volume
192
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.192 (2025)
Suggested Citation
Ariyadamrongkwan J., Muanprasat C. Pathophysiological mechanisms underlying diarrhea across generations of EGFR-TKIs: The role of ERBB signaling and potential therapies. Biomedicine and Pharmacotherapy Vol.192 (2025). doi:10.1016/j.biopha.2025.118562 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112266
Title
Pathophysiological mechanisms underlying diarrhea across generations of EGFR-TKIs: The role of ERBB signaling and potential therapies
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Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), a targeted therapy for the treatment of metastatic non-small cell lung cancer (NSCLC), improve patient outcomes compared to chemotherapy. Nevertheless, EGFR-TKIs are frequently associated with severe gastrointestinal toxicities, particularly diarrheas which often necessitate dose adjustments or treatment interruptions, thereby compromising therapeutic benefits. Current anti-diarrheal treatments are empirical and lack specificity, underscoring the need for a better understanding of the underlying mechanisms. This review highlights 3 key mechanisms underlying EGFR-TKI-induced diarrhea, emphasizing the role of ERBB signaling, including increased chloride secretion, enhanced intestinal epithelial permeability, and alterations in gut microbiota, which collectively contribute to the pathophysiology of diarrheas. The mechanisms contributing to diarrheas are discussed across different EGFR-TKI generations, with attention to their distinct receptor targets and the associated clinical prevalence of diarrheas. Potential therapeutic strategies are also categorized based on these underlying mechanisms, offering insights for effective management of EGFR-TKI-induced diarrheas.