Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems

Nathan P. Staff, Jill C. Fehrenbacher, Martial Caillaud, M. Imad Damaj, Rosalind A. Segal, Sandra Rieger

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

Paclitaxel (Brand name Taxol) is widely used in the treatment of common cancers like breast, ovarian and lung cancer. Although highly effective in blocking tumor progression, paclitaxel also causes peripheral neuropathy as a side effect in 60-70% of chemotherapy patients. Recent efforts by numerous labs have aimed at defining the underlying mechanisms of paclitaxel-induced peripheral neuropathy (PIPN). In vitro models using rodent dorsal root ganglion neurons, human induced pluripotent stem cells, and rodent in vivo models have revealed a number of molecular pathways affected by paclitaxel within axons of sensory neurons and within other cell types, such as the immune system and peripheral glia, as well skin. These studies revealed that paclitaxel induces altered calcium signaling, neuropeptide and growth factor release, mitochondrial damage and reactive oxygen species formation, and can activate ion channels that mediate responses to extracellular cues. Recent studies also suggest a role for the matrix-metalloproteinase 13 (MMP-13) in mediating neuropathy. These diverse changes may be secondary to paclitaxel-induced microtubule transport impairment. Human genetic studies, although still limited, also highlight the involvement of cytoskeletal changes in PIPN. Newly identified molecular targets resulting from these studies could provide the basis for the development of therapies with which to either prevent or reverse paclitaxel-induced peripheral neuropathy in chemotherapy patients.

Original languageEnglish (US)
Article number113121
JournalExperimental Neurology
Volume324
DOIs
StatePublished - Feb 2020
Externally publishedYes

Keywords

  • Human genetic studies
  • Inflammation
  • Intraepidermal nerve endings
  • Neuropathic pain
  • Paclitaxel-induced peripheral neuropathy
  • Reactive oxygen species
  • Small fiber neuropathy

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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