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Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI–Mediated Anticancer Activity in NSCLC
Yang,Zheng1; Chan,Kin Iong2,3; Kwok,Hang Fai1,2; Tam,Kin Yip1
2019-11-01
Source PublicationTranslational Oncology
Volume12Issue:11Pages:1516-1524
AbstractEpidermal growth factor receptor (EGFR) mutations were found in 30%-40% of non–small cell lung cancer (NSCLC) patients, who often responded well to EGFR tyrosine kinase inhibitors (EGFR-TKIs) as exemplified by erlotinib and gefitinib in the past decades. However, EGFR mutation-led drug resistance usually occurred upon prolonged treatment with EGFR-TKI. Herein, we study the anticancer effects of EGFR-TKI in combination with a newly developed antibody, A9(B8), to target a disintegrin and metalloprotease (ADAM) 17 that was overexpressed in NSCLC patients. NSCLC cell lines with different EGFR mutations were used to evaluate the drug combination. We have found that the EGFR-TKI-A9(B8) combination exhibited enhanced anticancer effects in NCI-H1975 cells harboring L858R and T790M mutations, which were due to simultaneous suppression of extracellular signal–regulated kinases phosphorylation. Our results suggested that targeting ADAM17 could potentiate the anticancer effects of EGFR-TKI against NSCLC and overcome drug resistance due to EGFR mutations.
DOI10.1016/j.tranon.2019.08.003
URLView the original
Language英語English
Scopus ID2-s2.0-85071025861
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorKwok,Hang Fai
Affiliation1.Cancer Centre,Faculty of Health Sciences,University of Macau,Macau SAR,Avenida de Universidade, Taipa,China
2.Centre for Precision Medicine Research and Training,Faculty of Health Sciences,University of Macau,Macau SAR,Avenida de Universidade, Taipa,China
3.Department of Pathology,Kiang Wu Hospital,Macau SAR,China
First Author AffilicationCancer Centre
Corresponding Author AffilicationCancer Centre;  Faculty of Health Sciences
Recommended Citation
GB/T 7714
Yang,Zheng,Chan,Kin Iong,Kwok,Hang Fai,et al. Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI–Mediated Anticancer Activity in NSCLC[J]. Translational Oncology,2019,12(11):1516-1524.
APA Yang,Zheng,Chan,Kin Iong,Kwok,Hang Fai,&Tam,Kin Yip.(2019).Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI–Mediated Anticancer Activity in NSCLC.Translational Oncology,12(11),1516-1524.
MLA Yang,Zheng,et al."Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI–Mediated Anticancer Activity in NSCLC".Translational Oncology 12.11(2019):1516-1524.
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