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TLR4/PKC‐mediated tight junction modulation: A clinical marker of chemotherapy‐induced gut toxicity?
Author(s) -
Wardill Hannah R.,
Gibson Rachel J.,
Logan Richard M.,
Bowen Joanne M.
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28656
Subject(s) - tight junction , chemotherapy , toxicity , toll like receptor , protein kinase c , tlr4 , signal transduction , medicine , biology , receptor , cancer research , bioinformatics , microbiology and biotechnology , innate immune system
Chemotherapy‐induced gut toxicity is a major clinical and economic burden to oncology practice. The mechanisms responsible for its development are ill defined, hampering the development of therapeutic interventions. In light of newly published research foci and clinical practice guidelines in supportive care in cancer, there has been renewed interest in the role tight junctions play in the pathobiology of chemotherapy‐induced gut toxicity. Several preclinical studies have identified molecular defects in intestinal tight junctions following chemotherapy. Despite these findings, the mechanisms responsible for chemotherapy‐induced tight junction disruption remain unclear. Recent research has highlighted roles for toll‐like receptor 4 and protein kinase C signalling in the regulation of tight junctions. This critical review therefore aims to provide evidence linking toll‐like receptor 4 expression, protein kinase C activation and tight junction disruption and their relationship to clinical toxicity.