Type

Journal Article

Authors

N O'Donovan
M Clynes
J Crown
B Corkery

Subjects

Biochemistry

Topics
drug effects breast neoplasms receptor erbb 2 antineoplastic combined chemotherapy protocols humans metabolism down regulation cell cycle inhibitory concentration 50 gefitinib proto oncogene proteins c akt female protein kinase inhibitors taxoids drug synergism egfr protein human signal transduction pathology dose response relationship drug cell line tumor mitogen activated protein kinases antagonists inhibitors receptor epidermal growth factor receptors estrogen pharmacology receptors progesterone docetaxel phosphorylation erbb2 protein human quinazolines carboplatin

Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. (2009)

Abstract No proven targeted therapy is currently available for the treatment of triple-negative breast cancer (TNBC). Epidermal growth factor receptor (EGFR) is frequently overexpressed in TNBC. We studied the activity of EGFR antagonists alone, and in combination with chemotherapy, in TNBC cell lines. EGFR and phosphorylated EGFR were measured by enzyme-linked immunosorbent assay. Sensitivity to EGFR inhibitors alone and in combination with chemotherapy was assessed. Effects of gefitinib on EGFR signalling and cell cycle were also examined. EGFR was overexpressed in the TNBC compared with the human epidermal growth factor receptor 2 (HER-2)-positive cell lines. Phosphorylation of EGFR was detected in the TNBC cells in response to epidermal growth factor stimulation and was blocked by gefitinib treatment. However, the TNBC cell lines were less sensitive to EGFR inhibition than the HER-2-positive cell lines. Response to gefitinib was associated with reduced phosphorylation of both mitogen activated protein kinase (MAPK) and Akt and induction of G(1) arrest. Gefitinib enhanced response to both carboplatin and docetaxel in the TNBC cells, and the triple combination of gefitinib, carboplatin and docetaxel was synergistic. Although the TNBC cells are less sensitive to EGFR inhibition than the HER-2-positive cell lines, gefitinib enhanced response to chemotherapy. Gefitinib combined with carboplatin and docetaxel warrants further investigation in TNBC.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

N O'Donovan, M Clynes, J Crown, B Corkery

Experts in our system

1
Norma O'Donovan
Dublin City University
Total Publications: 52
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
John Crown
Dublin City University