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Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non-small cell lung cancers
Doody J.F.; Wang Y.; Patel S.N.; Joynes C.; Sui P.L.; Gerlak J.; Rolser R.L.; Li Y.; Steiner P.; Bassi R.; Hicklin D.J.; Hadari Y.R.
2007-10-01
Source PublicationMolecular Cancer Therapeutics
ISSN15357163
Volume6Issue:10Pages:2642-2651
AbstractMutations in the kinase domain of the epidermal growth factor receptor (EGFR) were identified in ∼15% of all patients with non-small cell lung cancer (NSCLC). These mutations have been established as an indicator of superior response to gefitinib and erlotinib, small molecule inhibitors of the EGFR kinase domain. Whether these mutations would also render patients more susceptible to treatment with cetuximab (Erbitux), an EGFR-neutralizing antibody, is yet to be determined. In this study, we attempted to evaluate the effect of cetuximab on several NSCLC lines harboring some of the more common EGFRmutations (L858Rand delL747-T753insS), as well as the recently identified kinase inhibitor-resistant mutation, T790M. We could show that the kinase activity of the above mentioned EGFR mutants was hindered by cetuximab, as detected by both cell-based phosphorylation and proliferation assays. Interestingly, cetuximab also induced enhanced degradation of the EGFR mutants as compared with the wild-type receptor. Most importantly, cetuximab successfully inhibited the growth of NSCLC lines in xenograft models. These results indicate the promising potential of cetuximab as a regimen for patients with NSCLC bearing these mutations. Copyright © 2007 American Association for Cancer Research.
DOI10.1158/1535-7163.MCT-06-0506
URLView the original
Language英語
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Cited Times [WOS]:42   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
AffiliationEli Lilly and Company
Recommended Citation
GB/T 7714
Doody J.F.,Wang Y.,Patel S.N.,et al. Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non-small cell lung cancers[J]. Molecular Cancer Therapeutics,2007,6(10):2642-2651.
APA Doody J.F..,Wang Y..,Patel S.N..,Joynes C..,Sui P.L..,...&Hadari Y.R..(2007).Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non-small cell lung cancers.Molecular Cancer Therapeutics,6(10),2642-2651.
MLA Doody J.F.,et al."Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non-small cell lung cancers".Molecular Cancer Therapeutics 6.10(2007):2642-2651.
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