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Pharmacogenomics of thymidylate synthase in cancer treatment

Peter V Danenberg1

  • 1Department of Biochemistry and Molecular Biology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. pdanenbe@usc.edu

Frontiers in Bioscience : a Journal and Virtual Library
|September 9, 2004
PubMed

Insights

The thymidylate synthase (TS) gene polymorphism may predict cancer patient response to 5-fluorouracil (5-FU) chemotherapy. Further research is needed to clarify its role in treatment outcomes and toxicity.

Area of Science:

  • Pharmacogenomics
  • Cancer Therapeutics
  • Molecular Biology

Background:

  • 5-fluorouracil (5-FU) is a widely used cancer drug targeting thymidylate synthase (TS).
  • Tumor response to 5-FU is variable, and patients often experience drug toxicity.
  • High intratumoral TS levels generally correlate with poor response, while low levels suggest better outcomes.

Purpose of the Study:

  • To review pharmacogenomic studies investigating the association between a TS gene polymorphism and 5-FU treatment outcomes.
  • To elucidate the role of this genetic variation in TS expression, 5-FU efficacy, toxicity, and patient survival.

Main Methods:

  • Review of existing pharmacogenomic literature on the thymidylate synthase (TS) gene.
  • Analysis of studies examining the association between a 28 base-pair (bp) promoter polymorphism in the TS gene and clinical outcomes.

Main Results:

  • Data suggest a potential link between the TS gene polymorphism and TS expression levels.
  • The polymorphism's association with 5-FU response, toxicity, and survival is inconsistent across studies.
  • The predictive value of this TS polymorphism for treatment outcome remains unclear.

Conclusions:

  • The role of the TS gene polymorphism as a predictor of 5-FU treatment outcome requires further investigation.
  • Clarifying the function of this genetic polymorphism is crucial for personalized cancer therapy.
  • Ongoing evaluation is necessary to determine the clinical utility of this TS marker.

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