Type

Journal Article

Authors

N O'Donovan
D Slamon
M Clynes
M J Duffy
N Venkatesan
J Crown
B C Browne

Subjects

Pharmacology

Topics
genetics cell line tumor drug therapy antagonists inhibitors rna small interfering antibodies monoclonal biosynthesis trastuzumab receptor igf type 1 cell growth processes nvp aew541 combined modality therapy drug resistance neoplasm breast neoplasms transfection receptor erbb 2 enzymology pyrroles antibodies monoclonal humanized antineoplastic combined chemotherapy protocols therapy administration dosage metabolism humans protein kinase inhibitors drug synergism pyrimidines female therapeutic use drug effects

Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. (2010)

Abstract although trastuzumab has improved the prognosis for HER-2-positive breast cancer patients, not all HER-2-positive breast tumours respond to trastuzumab treatment and those that initially respond frequently develop resistance. Insulin-like growth factor-1 receptor (IGF1R) signalling has been previously implicated in trastuzumab resistance. We tested IGF1R inhibition to determine if dual targeting of HER-2 and IGF1R improves response in cell line models of acquired trastuzumab resistance. HER-2, IGF1R, phospho-HER-2, and phospho-IGF1R levels were measured by enzyme-linked immunosorbent assays in parental and trastuzumab-resistant SKBR3 and BT474 cells. IGF1R signalling was targeted in these cells using both small interfering RNA (siRNA) and the tyrosine kinase inhibitor, NVP-AEW541. IGF1R levels were significantly increased in the trastuzumab-resistant model, SKBR3/Tr, compared with the parental SKBR3 cell line. In both the SKBR3/Tr and BT474/Tr cell lines, inhibition of IGF1R expression with siRNA or inhibition of tyrosine kinase activity by NVP-AEW541 significantly increased response to trastuzumab. The dual targeting approach also improved response in the parental SKBR3 cells but not in the BT474 parental cells. our results confirm that IGF1R inhibition improves response to trastuzumab in HER-2-positive breast cancer cells and suggest that dual targeting of IGF1R and HER-2 may improve response in HER-2-positive tumours.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

N O'Donovan, D Slamon, M Clynes, M J Duffy, N Venkatesan, J Crown, B C Browne

Experts in our system

1
Norma O'Donovan
Dublin City University
Total Publications: 52
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
Michael J Duffy
University College Dublin
 
4
John Crown
Dublin City University
 
5
Brigid C Browne
Dublin City University
Total Publications: 8