Abstract | BACKGROUND: Human epidermal growth-factor receptor (HER)-2 is overexpressed in 25 % of breast- cancers and is associated with an aggressive form of the disease with significantly shortened disease free and overall survival. In recent years, the use of HER2-targeted therapies, monoclonal-antibodies and small molecule tyrosine-kinase inhibitors has significantly improved the clinical outcome for HER2-positive breast-cancer patients. However, only a fraction of HER2-amplified patients will respond to therapy and the use of these treatments is often limited by tumour drug insensitivity or resistance and drug toxicities. Currently there is no way to identify likely responders or rational combinations with the potential to improve HER2-focussed treatment outcome. METHODS: In order to further understand the molecular mechanisms of treatment-response with HER2-inhibitors, we used a highly-optimised and reproducible quantitative label-free LC-MS strategy to characterize the proteomes of HER2-overexpressing breast-cancer cell-lines (SKBR3, BT474 and HCC1954) in response to drug-treatment with HER2-inhibitors ( lapatinib, neratinib or afatinib). RESULTS: CONCLUSION: This proteomic study highlights several proteins that are closely associated with early HER2-inhibitor response and will provide a valuable resource for further investigation of ways to improve efficacy of breast-cancer treatment.
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Authors | Alessio Di Luca, Michael Henry, Paula Meleady, Robert O'Connor |
Journal | Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences
(Daru)
Vol. 23
Pg. 40
(Aug 04 2015)
ISSN: 2008-2231 [Electronic] Switzerland |
PMID | 26238995
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protein Kinase Inhibitors
- Quinazolines
- Quinolines
- Lapatinib
- Afatinib
- ERBB2 protein, human
- Receptor, ErbB-2
- neratinib
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Topics |
- Afatinib
- Breast Neoplasms
(metabolism)
- Cell Line, Tumor
- Chromatography, Liquid
- Female
- Humans
- Lapatinib
- Mass Spectrometry
- Protein Kinase Inhibitors
(pharmacology)
- Proteomics
- Quinazolines
(pharmacology)
- Quinolines
(pharmacology)
- Receptor, ErbB-2
(antagonists & inhibitors)
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