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[Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Contributes to Tamoxifen Resistance in Estrogen-Positive

T A Dronova1,2,3, N N Babyshkina1,2,4, M V Zavyalova1,4

  • 1Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634009 Russia.

Molekuliarnaia Biologiia
|February 10, 2021
PubMed

Insights

Genetic variants in the KDR gene, specifically rs2305948, may predict tamoxifen treatment success in breast cancer patients. This finding offers potential for personalized therapy by identifying patients likely to benefit from tamoxifen.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Estrogen receptor (ER) and vascular endothelial growth factor receptor type II (VEGFR2) signaling crosstalk contributes to tamoxifen resistance in breast cancer.
  • High VEGFR2 expression is a known marker for tamoxifen resistance.
  • The prognostic significance of VEGFR2/KDR gene polymorphisms for tamoxifen efficacy is not well-established.

Purpose of the Study:

  • To investigate the prognostic value of KDR gene functional polymorphisms (rs2071559 and rs2305948) and KDR gene expression levels in breast cancer patients undergoing tamoxifen therapy.
  • To determine if specific KDR genotypes are associated with tamoxifen treatment response and patient survival.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) was used to genotype KDR variants (rs2071559, rs2305948) and measure KDR mRNA levels in 122 breast tumor samples.
  • Immunohistochemistry was employed to assess VEGFR2 protein expression.
  • Patients were categorized into groups based on progression (metastases or relapse) versus no progression during tamoxifen therapy.

Main Results:

  • The frequency of heterozygous and mutant genotypes for the KDR rs2305948 single nucleotide polymorphism (SNP) was significantly higher in patients who did not progress on tamoxifen compared to those who did.
  • The KDR rs2305948 polymorphism was associated with improved survival rates in breast cancer patients.
  • A correlation between ESR1 and KDR mRNA levels was observed in patients who responded well to tamoxifen.

Conclusions:

  • The KDR rs2305948 polymorphism demonstrates prognostic value, potentially indicating sensitivity to tamoxifen therapy.
  • This genetic marker may contribute to understanding the tumor phenotype related to tamoxifen response.
  • Further research could explore the clinical utility of KDR rs2305948 in guiding tamoxifen treatment decisions for breast cancer patients.
Keywords:
breast cancerestrogen receptorgene expressionsingle nucleotide polymorphismstamoxifen resistancevascular endothelial growth factor receptor type II (VEGFR2)

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