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The Predictive Value of Epidermal Growth Factor Receptor Expression for Sensitivity to Vinorelbine in Breast Cancer
- Source :
- Basic & Clinical Pharmacology & Toxicology. 109:499-505
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- Breast cancer patients with positive epidermal growth factor receptor (EGFR) expression have significantly worse post-relapse prognosis than patients with negative EGFR expression. Vinorelbine (NVB) is usually reserved as a salvage therapy after anthracyclines and taxanes in patients with breast cancer. To see whether EGFR expression has a predictive value in NVB-mediated effect on human breast cancer cells, we examined 50 primary breast cancer samples. Of these, 42% were found to be NVB sensitive by ATP-tumour chemosensitivity assay. Sensitivity was correlated with EGFR expression level (p = 0.001). To dynamically examine EGFR's effect on NVB sensitivity in breast cancer cells, we used the real-time cell electronic sensing system with EGFR-positive and EGFR-negative breast cancer cell lines, MCF-7 and MDA-MB-435s, respectively. MCF-7 is NVB sensitive, while MDA-MB-435 is NVB resistant. NVB-induced cytotoxicity to MCF-7 can be partly reversed with inhibitory anti-EGFR antibody. NVB up-regulated EGFR expression in MCF-7 cells, which affects ERK1/2 phosphorylation. This cellular response mechanism may cause greater input to non-lethally damaged cells. These data suggest that EGFR expression can be used as a prognostic factor for breast cancer sensitivity to NVB, which could help identify appropriate treatments for breast cancer.
- Subjects :
- Pharmacology
Oncology
medicine.medical_specialty
biology
business.industry
Cell
General Medicine
Toxicology
Vinorelbine
medicine.disease
Vinblastine
medicine.anatomical_structure
Breast cancer
Internal medicine
Cancer cell
medicine
biology.protein
Immunohistochemistry
Epidermal growth factor receptor
skin and connective tissue diseases
business
Chemosensitivity assay
medicine.drug
Subjects
Details
- ISSN :
- 17427835
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Basic & Clinical Pharmacology & Toxicology
- Accession number :
- edsair.doi...........d5e8021849423df44d24abe734645af2
- Full Text :
- https://doi.org/10.1111/j.1742-7843.2011.00759.x