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Updated: Apr 11, 2026

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice
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Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy

Masaaki Komatsu1, Heather E Wheeler1, Suyoun Chung2

  • 1Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 28, 2015
PubMed
Abstract

Insights

Genetic variations influence paclitaxel-induced peripheral neuropathy. This study identified AIPL1 and BCR genes associated with paclitaxel sensitivity, offering insights into predicting and preventing this common chemotherapy side effect.

Area of Science:

  • Pharmacogenomics
  • Neuroscience
  • Oncology

Background:

  • Paclitaxel is a vital chemotherapy agent for various cancers, but its use is limited by unpredictable sensory peripheral neuropathy.
  • Identifying genetic factors influencing neuropathy risk is crucial for personalized cancer treatment.

Purpose of the Study:

  • To investigate the role of germline genetic variations in paclitaxel-induced peripheral neuropathy using an integrative approach.
  • To identify and functionally validate genes contributing to paclitaxel cytotoxicity and neuropathy.

Main Methods:

  • Genome-wide association studies (GWAS) were conducted on paclitaxel-induced cytotoxicity in lymphoblastoid cell lines (LCLs) and neuropathy in Asian patients.
  • A gene-based analysis identified overlapping genes between LCL cytotoxicity and patient neuropathy, with comparisons to a European cohort.
  • Human-induced pluripotent stem cell-derived neurons were used for functional validation of candidate genes like AIPL1 and BCR.

Main Results:

  • Single nucleotide polymorphisms (SNPs) near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs.
  • Decreased AIPL1 expression reduced neuronal sensitivity to paclitaxel, altering neurite morphology.
  • A gene-based analysis revealed 32 overlapping genes, including BCR, between Asian LCL cytotoxicity and patient neuropathy. BCR knockdown increased neuronal sensitivity to paclitaxel.

Conclusions:

  • Genetic variants associated with paclitaxel-induced cytotoxicity in Asian populations were identified.
  • AIPL1 and BCR were functionally validated as key genes influencing neuronal response to paclitaxel.
  • An integrative pharmacogenomics approach combining LCL and patient GWAS can prioritize genes for chemotherapeutic-induced peripheral neuropathy research.

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