Journal
TRANSLATIONAL ONCOLOGY
Volume 12, Issue 11, Pages 1516-1524Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2019.08.003
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Funding
- Science and Technology Development Fund, Macau SAR [0055/2019/A1]
- Faculty of Health Sciences, University of Macau
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Epidermal 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(138) 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.
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