title: ErbB small molecule tyrosine kinase inhibitor (TKI) induced diarrhoea: Chloride secretion as a mechanistic hypothesis.
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.
authors.affiliation: 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: ysabella.vansebille@adelaide.edu.au.
authors.forename: Ysabella Z A
authors.initials: YZ
authors.lastname: Van Sebille
authors.affiliation: School of Medical Sciences, Discipline of Anatomy and Pathology, University of Adelaide, Australia.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Gibson
authors.affiliation: School of Medical Sciences, Discipline of Physiology, University of Adelaide, Australia; School of Medical Sciences, Discipline of Anatomy and Pathology, University of Adelaide, Australia.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Wardill
authors.affiliation: School of Medical Sciences, Discipline of Physiology, University of Adelaide, Australia.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Bowen
mesh_terms: D003967:Diarrhea / Q000209:etiology*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D020893:Receptor, ErbB-3 / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D012965:Sodium Chloride / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D012965:Sodium Chloride; D020893:Receptor, ErbB-3
keywords: Chloride secretion; Diarrhoea; ErbB (EGFR, HER); Mucositis; TKI