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Central neurotoxicity in cancer chemotherapy: pharmacogenetic insights

Femke E A M Froklage1, Jaap C Reijneveld, Jan J Heimans

  • 1VU University Medical Center, Department of Neurology, Amsterdam, The Netherlands. f.froklage@vumc.nl

Pharmacogenomics
|April 1, 2011
PubMed

Insights

Genetic factors may influence chemotherapy-induced neurotoxicity risk. Research reviews polymorphisms in folate metabolism, apolipoprotein E, and blood-brain barrier transporters, highlighting the need for larger studies to clarify pharmacogenetics roles.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Chemotherapy-induced neurotoxicity is a complex condition with multifactorial origins.
  • Two primary hypotheses for endogenous mechanisms include the target hypothesis and the blood-brain barrier transporter hypothesis.

Purpose of the Study:

  • To review candidate genetic determinants contributing to the risk of chemotherapy-induced neurotoxicity.
  • To explore the role of polymorphisms in target mechanisms and blood-brain barrier transporters.

Main Methods:

  • Review of existing literature on genetic polymorphisms associated with chemotherapy neurotoxicity.
  • Focus on polymorphisms in folate metabolizing enzymes, apolipoprotein E, and blood-brain barrier transporter genes.

Main Results:

  • Candidate genetic determinants, including specific polymorphisms, are implicated in chemotherapy neurotoxicity.
  • The precise role of pharmacogenetics in the mechanisms of central neurotoxicity remains incompletely understood.

Conclusions:

  • Larger, prospective, longitudinal, and uniform studies are essential for a comprehensive understanding.
  • Future research should incorporate pre-chemotherapy and follow-up assessments of neuropsychological performance, neuroimaging (MRI, PET), genetic profiles, and relevant biomarkers.

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