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Updated: Oct 7, 2025

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The impact of SBF2 on taxane-induced peripheral neuropathy

Geneva M Cunningham1, Fei Shen2, Xi Wu2

  • 1Department of Medical and Molecular Genetics, Indiana University School of Medicine; Indianapolis, Indiana, United States of America.

Plos Genetics
|January 5, 2022
PubMed

Insights

SET-Binding Factor 2 (SBF2) mutations worsen taxane-induced peripheral neuropathy (TIPN). This study shows SBF2 knockdown exacerbates neuronal damage, offering insights into TIPN development and potential therapeutic targets.

Area of Science:

  • Neuroscience
  • Genetics
  • Oncology

Background:

  • Taxane-induced peripheral neuropathy (TIPN) is a significant challenge in cancer survivorship, affecting quality of life and treatment efficacy.
  • Health disparities exist, with African Americans (AA) disproportionately affected by severe TIPN.
  • Previous research linked SET-Binding Factor 2 (SBF2) mutations to severe TIPN in AA patients.

Purpose of the Study:

  • To investigate the role of SBF2 in taxane-induced neuronal damage using an ex vivo model.
  • To elucidate the molecular mechanisms underlying SBF2's impact on TIPN.

Main Methods:

  • Utilized an ex vivo model employing induced pluripotent stem cell-derived sensory neurons with SBF2 knockdown.
  • Assessed the effects of paclitaxel on neuronal viability, neurite outgrowth, and sodium current.
  • Analyzed paclitaxel-induced gene expression changes in mature sensory neurons.

Main Results:

  • SBF2 knockdown exacerbated paclitaxel-induced reductions in cell viability and neurite outgrowth.
  • Knockdown of SBF2 attenuated paclitaxel-induced inhibition of sodium currents.
  • Identified specific gene expression changes in mature sensory neurons related to paclitaxel treatment and SBF2 knockdown.

Conclusions:

  • Provided ex vivo evidence supporting SBF2's role in the development of TIPN.
  • Identified potential candidate genes and pathways involved in the exacerbation of TIPN phenotypes.
  • Findings may inform strategies to mitigate TIPN and address health disparities.

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