CXCR4, a potential predictive marker for docetaxel sensitivity in gastric cancer

Anticancer Res. 2010 Jun;30(6):2209-16.

Abstract

The aim of this study was to explore predictive genes involved in docetaxel sensitivity of gastric cancer.

Materials and methods: Microarray analysis was performed to explore various gene expression levels between parental and docetaxel-resistant cells. A panel of 11 genes selected according to microarray analysis were validated and tested further in 11 cancer cell lines, resulting in 4 genes, CXCR4, CDK6, USP15 and CDH1. Histoculture drug response assay (HDRA) was used to examine docetaxel sensitivity, while qRT-PCR was used to measure the mRNA levels of the genes in 25 surgically dissected gastric cancer specimens.

Results: Only CXCR4 mRNA levels in gastric cancer tissues were correlated with docetaxel sensitivity (R(2)=0.23, p=0.019) and significantly higher in resistant specimens (p=0.038). AMD3100, a CXCR4 antagonist, enhanced the docetaxel cytotoxicity in vitro.

Conclusion: CXCR4 mRNA expression levels may be a potential predictive biomarker in gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzylamines
  • Biomarkers
  • Cell Line, Tumor
  • Cyclams
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Gene Expression Profiling
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / physiology*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Taxoids / pharmacology*

Substances

  • Benzylamines
  • Biomarkers
  • CXCR4 protein, human
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • Taxoids
  • Docetaxel
  • plerixafor