Type

Journal Article

Authors

John Crown
William M Gallagher
Sharon McGee
Aisling E O'Connor
Annette T Byrne
Norma O'Donovan

Subjects

Pharmacology

Topics
antineoplastic combined chemotherapy protocols xenograft model antitumor assays gefitinib trastuzumab immunoblotting enzymology animals drug synergism cell proliferation mice drug effects therapeutic use breast neoplasms antagonists inhibitors receptor erbb 2 humans receptor epidermal growth factor female inhibitory concentration 50 quinazolines drug therapy molecular targeted therapy lapatinib metabolism protein kinase inhibitors pathology cell line tumor antibodies monoclonal humanized pharmacology mice inbred balb c

Synergistic interaction between trastuzumab and EGFR/HER-2 tyrosine kinase inhibitors in HER-2 positive breast cancer cells. (2010)

Abstract Overexpression of HER-2 in breast cancer is frequently associated with expression of EGFR, and EGFR expression influences response to HER-2 inhibition. The aim of this study was to examine the effects of combining dual inhibition of EGFR and HER-2, using trastuzumab, gefitinib and lapatinib, in HER-2 overexpressing breast cancer cells. Combination proliferation assays were performed in two HER-2 positive breast cancer cell lines, SKBR-3 and BT-474. Trastuzumab combined with lapatinib was also tested in BT-474 xenografts. In proliferation assays, dual targeting with trastuzumab and gefitinib or lapatinib showed synergy or additivity in both SKBR-3 and BT-474 cells. Trastuzumab (10 nM) or gefitinib (5 µM) alone did not induce significant apoptosis, whereas lapatinib (0.75 µM) induced significant apoptosis in SKBR-3 cells. Trastuzumab combined with lapatinib further enhanced apoptosis induction. Trastuzumab (10 nM) and gefitinib (5 µM) induced apoptosis comparable to lapatinib alone (0.75 µM), suggesting that inhibition of both EGFR and HER-2 may be required to induce apoptosis in these cells. Pre-treatment with trastuzumab and gefitinib or lapatinib enhanced response to chemotherapy in vitro. The combination of trastuzumab and lapatinib also effectively blocked tumour growth in vivo. Dual targeting of EGFR and HER-2, by combining trastuzumab with EGFR/HER-2 tyrosine kinase inhibitors, may improve response in HER-2 overexpressing breast cancer cells that also express EGFR.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

John Crown, William M Gallagher, Sharon McGee, Aisling E O'Connor, Annette T Byrne, Norma O'Donovan

Experts in our system

1
John Crown
Dublin City University
Total Publications: 104
 
2
William M Gallagher
University College Dublin
Total Publications: 148
 
3
Annette T Byrne
Royal College of Surgeons in Ireland
Total Publications: 41
 
4
Norma O'Donovan
Dublin City University
Total Publications: 59