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

Raja Nur Firzanah Syaza Raja Sharin1, Jesmine Khan1, Mohamad Johari Ibahim1

  • 1Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.

Biomed Research International
|July 8, 2022
PubMed

Insights

Lapatinib causes diarrhea in breast cancer patients by inhibiting ErbB1 in the gut. This review explores how ErbB1 impacts gut health, leading to this common side effect.

Area of Science:

  • Oncology
  • Gastroenterology
  • Pharmacology

Background:

  • Lapatinib, a small-molecule tyrosine kinase inhibitor (SM-TKI), effectively treats ErbB2-positive breast cancer.
  • Gastrointestinal toxicity, particularly diarrhea, is a significant adverse effect limiting lapatinib's use and impacting patient quality of life.
  • Lapatinib inhibits both ErbB1 and ErbB2; ErbB1 is highly expressed in the gut epithelium, suggesting its role in lapatinib-induced diarrhea.

Purpose of the Study:

  • To review the potential mechanisms underlying lapatinib-induced diarrhea.
  • To investigate the specific role of ErbB1 inhibition in the development of lapatinib-induced gastrointestinal toxicity.
  • To explore how ErbB1 modulation affects gut homeostasis, inflammation, and intestinal permeability.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of pharmacological data on lapatinib's targets and effects.
  • Synthesis of evidence linking ErbB1 signaling to gut pathophysiology.

Main Results:

  • Lapatinib's dual inhibition of ErbB1 and ErbB2 is implicated in its gastrointestinal side effects.
  • ErbB1 inhibition may disrupt normal gut epithelial function and homeostasis.
  • Evidence suggests ErbB1's involvement in lapatinib-induced inflammation and increased intestinal permeability.

Conclusions:

  • ErbB1 inhibition is a likely contributor to lapatinib-induced diarrhea.
  • Understanding these mechanisms can inform strategies to mitigate this adverse effect.
  • Further research into ErbB1's role in gut health is warranted for targeted cancer therapy optimization.

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