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Related Experiment Videos

Predicting drug response and toxicity based on gene polymorphisms.

Jacques Robert1, Valérie Le Morvan, Denis Smith

  • 1Institut Bergonié and Université Victor Segalen Bordeaux 2, 229 cours de l'Argonne, 33076 Bordeaux-Cedex, France. robert@bergonie.org

Critical Reviews in Oncology/Hematology
|May 14, 2005
PubMed
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Gene variations, or polymorphisms, significantly impact how individuals respond to chemotherapy drugs. Identifying these genetic differences can personalize cancer treatment for better efficacy and reduced toxicity.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Human genome sequencing reveals numerous gene polymorphisms, particularly single nucleotide polymorphisms (SNPs).
  • These genetic variations can alter the function of drug-metabolizing enzymes, transporters, and drug targets.
  • Altered protein function due to polymorphisms can affect drug efficacy and toxicity, especially in chemotherapy.

Purpose of the Study:

  • To review identified polymorphisms in genes related to anticancer drug activity.
  • To highlight polymorphisms crucial for predicting drug toxicity and response in cancer patients.
  • To differentiate the role of polymorphisms in cancer risk versus drug response.

Main Methods:

  • Literature review of identified gene polymorphisms involved in anticancer drug activity.

Related Experiment Videos

  • Analysis of the impact of specific polymorphisms on drug metabolism, transport, and target interaction.
  • Evaluation of the clinical relevance of polymorphisms for predicting chemotherapy outcomes.

    • Main Results:

    • Functional polymorphisms in genes like thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD) are critical for predicting toxicity of 6-mercaptopurine and fluorouracil, respectively.
    • Common SNPs in glutathione S-transferase P1 (GSTP1) and xeroderma pigmentosum group D (XPD) are determinants of oxaliplatin activity.
    • The review consolidates knowledge on key genetic variations influencing anticancer drug efficacy and toxicity.

    Conclusions:

    • Identifying functional polymorphisms in cancer patients can guide personalized chemotherapy regimens.
    • Routine determination of specific polymorphisms (e.g., TPMT, DPD) is recommended for optimizing drug administration and minimizing adverse events.
    • Distinguishing the influence of polymorphisms on drug response from their role in cancer risk is essential for accurate clinical application.