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Tumor Biology
Published in: Tumor Biology 4/2015

01-04-2015 | Research Article

Acquired resistance to EGFR tyrosine kinase inhibitor in A431 squamous cell carcinoma xenografts is mediated by c-Kit pathway transduction

Authors: Lixia Zhang, Xiaokun Yang, Bei Zhao, Zhen Cai

Published in: Tumor Biology | Issue 4/2015

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Abstract

Epidermal growth factor inhibitors (EGFRIs), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, all responding patients eventually developed acquired resistance to EGFRIs and the mechanisms of acquired resistance invariably develops. In the current study, we reported the tumor xenografts of the human A431 squamous cell carcinoma, after 25-week consecutive therapy with EGFR inhibitor (gefitinib) that developed resistance as a result of c-Kit overexpression. Moreover, combined therapeutic inhibition of EGFR and c-Kit may abrogate this acquired mechanism of drug resistance due to an enhanced apoptotic effect in gefitinib-resistant xenograft model. Taken together, the results suggest that at least in the A431 xenograft model displaying acquired resistance to gefitinib can emerge in vivo, at least in part, by mechanisms involving the c-Kit overexpression.
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Metadata
Title
Acquired resistance to EGFR tyrosine kinase inhibitor in A431 squamous cell carcinoma xenografts is mediated by c-Kit pathway transduction
Authors
Lixia Zhang
Xiaokun Yang
Bei Zhao
Zhen Cai
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2932-7

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