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Discovery of genetic profiles impacting response to chemotherapy: application to gemcitabine

Hamdi Jarjanazi1, Jeffrey Kiefer, Sevtap Savas

  • 1Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.

Human Mutation
|March 12, 2008
PubMed

Insights

This study introduces a new method using NCI60 cell line data to find genetic markers linked to chemotherapy response. The approach identified specific genetic variations associated with gemcitabine drug response, aiding personalized cancer treatment.

Area of Science:

  • Genomics
  • Pharmacology
  • Cancer Research

Background:

  • Chemotherapy is a cornerstone of cancer treatment, but patient response varies significantly.
  • Genome-based technologies are emerging for identifying genes related to drug response, yet large-scale applications remain limited.

Purpose of the Study:

  • To develop and apply a novel strategy for discovering genetic variants associated with variable chemotherapy response.
  • To identify candidate genetic markers and haplotypes impacting gemcitabine pharmacobiology using NCI60 cell line data.

Main Methods:

  • Utilized genetic and drug response data from the NCI60 cancer cell line panel.
  • Performed single-nucleotide polymorphism (SNP) association analyses on candidate genes.
  • Conducted haplotype-based analyses to investigate the combined effects of SNPs.

Main Results:

  • Identified four SNPs within CDC5L, EPC2, POLS, and PARP1 associated with gemcitabine response.
  • Found modest associations for haplotypes in six genes, with a significant association in the POLS gene.
  • Demonstrated the utility of the NCI60 cell line screen for hypothesis generation.

Conclusions:

  • The novel strategy effectively identifies genes associated with drug response, applicable to other NCI60-profiled drugs.
  • The findings provide a basis for designing improved clinical trials and enabling individualized chemotherapy.
  • This approach facilitates the discovery of genetic markers for predicting patient response to chemotherapeutic agents.

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