Toll-like receptor 4 signaling: a common biological mechanism of regimen-related toxicities: an emerging hypothesis for neuropathy and gastrointestinal toxicity

Hannah R Wardill; Ysabella Z A Van Sebille; Kimberley A Mander; Rachel J Gibson; Richard M Logan; Joanne M Bowen; Stephen T Sonis

doi:10.1016/j.ctrv.2014.11.005

Toll-like receptor 4 signaling: a common biological mechanism of regimen-related toxicities: an emerging hypothesis for neuropathy and gastrointestinal toxicity

Cancer Treat Rev. 2015 Feb;41(2):122-8. doi: 10.1016/j.ctrv.2014.11.005. Epub 2014 Dec 5.

Authors

Hannah R Wardill¹, Ysabella Z A Van Sebille², Kimberley A Mander³, Rachel J Gibson⁴, Richard M Logan⁵, Joanne M Bowen⁶, Stephen T Sonis⁷

Affiliations

¹ Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, South Australia, Australia. Electronic address: [email protected].
² Discipline of Physiology, School of Medical Sciences, University of Adelaide, South Australia, Australia. Electronic address: [email protected].
³ Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, South Australia, Australia. Electronic address: [email protected].
⁴ Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, South Australia, Australia. Electronic address: [email protected].
⁵ School of Dentistry, University of Adelaide, South Australia, Australia. Electronic address: [email protected].
⁶ Discipline of Physiology, School of Medical Sciences, University of Adelaide, South Australia, Australia. Electronic address: [email protected].
⁷ Brigham and Women's Hospital, Boston, MA, USA. Electronic address: [email protected].

PMID: 25512119
DOI: 10.1016/j.ctrv.2014.11.005

Abstract

Regimen-related toxicities remain a priority concern within the field of supportive care in cancer. Despite this, many forms of toxicity are under reported and consequently poorly characterised. Although there have been significant improvements in our understanding of regimen-related toxicities, symptom management continues to occur independently raising concerns such as drug interactions and the tendency to emphasise management of a single symptom at the expense of others. This review focuses on two important toxicities induced by chemotherapy; neuropathy/pain and gastrointestinal toxicity, introducing the Toll-like receptor (TLR) 4 pathway as a common component of their pathobiology. Given the global observation of toxicity clusters, identification of a common initiating factor provides an excellent opportunity to simultaneously target multiple side effects of anticancer treatment. Furthermore, identification of common biological underpinnings could perhaps reduce polypharmacy and have pharmacoeconomic benefits.

Keywords: Chemotherapy; Glial activation; Gut toxicity; Neuropathy; Neurotoxicity; Toll-like receptor 4.

Publication types

Review

MeSH terms

Antineoplastic Agents / adverse effects*
Gastrointestinal Diseases / chemically induced*
Gastrointestinal Diseases / metabolism
Humans
NF-kappa B / metabolism
Neuroglia / metabolism*
Peripheral Nervous System Diseases / chemically induced*
Peripheral Nervous System Diseases / metabolism
Peripheral Nervous System Diseases / pathology
Polymorphism, Single Nucleotide
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*
Toll-Like Receptor 4 / drug effects
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism*

Substances

Antineoplastic Agents
NF-kappa B
Reactive Oxygen Species
TLR4 protein, human
Toll-Like Receptor 4