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Paclitaxel-induced neuropathy: potential association of MAPT and GSK3B genotypes

Susanna B Park, John B Kwok, Clement T Loy

  • 1Brain and Mind Research Institute, University of Sydney, Sydney, Australia. matthew.kiernan@sydney.edu.au.

BMC Cancer
|December 24, 2014
PubMed
Abstract

Insights

Genetic variations in tau-associated genes, like GSK-3B, may increase the risk of paclitaxel-induced peripheral neurotoxicity. Further studies are needed to confirm these findings in larger patient groups.

Area of Science:

  • Neuroscience
  • Pharmacogenetics
  • Oncology

Background:

  • Paclitaxel chemotherapy can cause dose-limiting peripheral neurotoxicity, impacting patient outcomes.
  • Genetic factors may influence an individual's susceptibility to this neurotoxicity.
  • The tau-microtubule pathway is a key target of paclitaxel and implicated in neurotoxicity.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in tau-associated genes and paclitaxel-induced neurotoxicity.
  • To identify specific genetic markers that predict the risk of developing neurotoxicity during paclitaxel treatment.

Main Methods:

  • Genotyping of polymorphisms in the microtubule-associated protein tau (MAPT) gene (haplotype 1, rs242557) and GSK-3β gene (rs6438552).
  • Assessment of paclitaxel-induced neurotoxicity using standardized neuropathy grading scales, neurophysiological tests, and patient-reported questionnaires.
  • Analysis of 21 patients undergoing paclitaxel treatment.

Main Results:

  • A statistically significant association was found between the GSK-3B rs6438552 polymorphism and the development of paclitaxel-induced neurotoxicity.
  • The study identified a potential genetic predictor for paclitaxel neurotoxicity.

Conclusions:

  • Genetic variations in tau-associated genes, particularly GSK-3B, may play a role in paclitaxel-induced neurotoxicity.
  • These findings suggest a potential role for pharmacogenetic screening in managing paclitaxel treatment.
  • Larger studies are required to validate these preliminary results and confirm the clinical utility.

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