ErbB small molecule tyrosine kinase inhibitor (TKI) induced diarrhoea: Chloride secretion as a mechanistic hypothesis

Ysabella Z A Van Sebille; Rachel J Gibson; Hannah R Wardill; Joanne M Bowen

doi:10.1016/j.ctrv.2015.05.011

ErbB small molecule tyrosine kinase inhibitor (TKI) induced diarrhoea: Chloride secretion as a mechanistic hypothesis

Cancer Treat Rev. 2015 Jul;41(7):646-52. doi: 10.1016/j.ctrv.2015.05.011. Epub 2015 Jun 6.

Authors

Ysabella Z A Van Sebille¹, Rachel J Gibson², Hannah R Wardill³, Joanne M Bowen⁴

Affiliations

¹ School of Medical Sciences, Discipline of Physiology, University of Adelaide, Australia; School of Medical Sciences, Discipline of Anatomy and Pathology, University of Adelaide, Australia. Electronic address: [email protected].
² School of Medical Sciences, Discipline of Anatomy and Pathology, University of Adelaide, Australia.
³ School of Medical Sciences, Discipline of Physiology, University of Adelaide, Australia; School of Medical Sciences, Discipline of Anatomy and Pathology, University of Adelaide, Australia.
⁴ School of Medical Sciences, Discipline of Physiology, University of Adelaide, Australia.

PMID: 26073491
DOI: 10.1016/j.ctrv.2015.05.011

Abstract

Diarrhoea is a common, debilitating and potentially life threatening toxicity of many cancer therapies. While the mechanisms of diarrhoea induced by traditional chemotherapy have been the focus of much research, the mechanism(s) of diarrhoea induced by small molecule ErbB TKI, have received relatively little attention. Given the increasing use of small molecule ErbB TKIs, identifying this mechanism is key to optimal cancer care. This paper critically reviews the literature and forms a hypothesis that diarrhoea induced by small molecule ErbB TKIs is driven by intestinal chloride secretion based on the negative regulation of chloride secretion by ErbB receptors being disrupted by tyrosine kinase inhibition.

Keywords: Chloride secretion; Diarrhoea; ErbB (EGFR, HER); Mucositis; TKI.

Publication types

Review

MeSH terms

Diarrhea / etiology*
Humans
Protein Kinase Inhibitors / adverse effects*
Protein Kinase Inhibitors / therapeutic use
Receptor, ErbB-3 / adverse effects*
Receptor, ErbB-3 / antagonists & inhibitors
Sodium Chloride / metabolism*

Substances

Protein Kinase Inhibitors
Sodium Chloride
Receptor, ErbB-3