Abstract | INTRODUCTION: METHODS: Two IBC cell lines SUM149 and FC-IBC-02 derived from pleural effusion of an IBC patient were used in this study. Cell growth and apoptotic cell death were examined in vitro. For the in vivo tumor growth studies, IBC cells were orthotopically transplanted into the mammary fat pads of immunodeficient mice. AZD8931 was given by daily oral gavage at doses of 25 mg/kg, 5 days/week for 4 weeks. Paclitaxel was subcutaneously injected twice weekly. RESULTS:
AZD8931 significantly suppressed cell growth of IBC cells and induced apoptosis of human IBC cells in vitro. Significantly, we showed that AZD8931 monotherapy inhibited xenograft growth and the combination of paclitaxel + AZD8931 was demonstrably more effective than paclitaxel or AZD8931 alone treatment at delaying tumor growth in vivo in orthotopic IBC models. CONCLUSION:
AZD8931 single agent and in combination with paclitaxel demonstrated signal inhibition and antitumor activity in EGFR-overexpressed and HER2 non-amplified IBC models. These results suggest that AZD8931 may provide a novel therapeutic strategy for the treatment of IBC patients with HER2 non-amplified tumors.
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Authors | Zhaomei Mu, Teresa Klinowska, Xiaoshen Dong, Emily Foster, Chris Womack, Sandra V Fernandez, Massimo Cristofanilli |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 33
Pg. 47
(May 30 2014)
ISSN: 1756-9966 [Electronic] England |
PMID | 24886365
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- AZD 8931
- Antineoplastic Agents
- Quinazolines
- EGFR protein, human
- ERBB2 protein, human
- ERBB3 protein, human
- ErbB Receptors
- Receptor, ErbB-2
- Receptor, ErbB-3
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- ErbB Receptors
(antagonists & inhibitors, metabolism)
- Female
- Gene Amplification
- Humans
- Inflammatory Breast Neoplasms
(drug therapy, metabolism)
- Mice
- Mice, SCID
- Quinazolines
(pharmacology, therapeutic use)
- Receptor, ErbB-2
(genetics, metabolism)
- Receptor, ErbB-3
(metabolism)
- Signal Transduction
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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