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Interview with Rachel Gibson at MASCC 2016: Is the mechanism responsible for gut toxicity, nerve toxicity and pain during chemotherapy the Toll-Like Receptor 4 pathway?

MASCC Interview 5 Rachel Gibson

Rachel Gibson is Professor and Dean of Academic Health Sciences at the University of South Australia. She discusses the Toll-Like Receptor 4 (TLR 4) pathway and its implication in gut toxicity and pain. Diarrhea occurs in approximately 10% of patients with advanced cancer as a result of chemotherapy-induced damage. To date, the mechanism responsible is poorly defined, which makes it difficult to treat. Prof Gibson discusses how commensal bacteria change during chemotherapy to pathogenic bacteria, which produce lipopolysaccharide—a major driver of TLR 4. She reviews the symptom cluster (gut toxicity, gut pain and nerve pain), that is associated with TLR 4 overexpression and discusses blocking TLR 4 expression in cell culture and in removing the TLR 4 gene in a mouse model. The knock-out mouse model was assessed for normal functioning and compared to wild type mouse in terms of diarrhea symptoms following chemotherapy. Prof Gibson highlights the switch from evaluating treatment-related symptoms on an individual basis to assessing them as a cluster of symptoms using a more holistic approach; an approach that can impact positively on polypharmacy and pharmcoeconomics. Dr Gibson is confident that the planning for a clinical trial will begin in the next 12 months, and that ultimately chemotherapy-induced diarrhea and gut and nerve pain will be effectively controlled to help increase health-related quality of life in patients experiencing these distressing symptoms.

This interview was recorded at the June 2016 annual meeting of MASCC in Adelaide Australia. It was conducted by medical writer Rhonda Oshanek.

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