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

• The mechanisms of ErbB TKI-induced diarrhoea are likely different to chemotherapy.
• This paper provides rationale for chloride secretion as a mechanistic hypothesis.
• This paper reviews current management of ErbB TKI-induced diarrhoea.
• This paper speculates on potential new therapies for ErbB TKI-induced diarrhoea.

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.