MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling

By J. Engelman, K. Zejnullahu, T. Mitsudomi, Youngchul Song, Courtney Hyland, Joon-Oh Park, N. Lindeman, Christopher-Michael Gale, Xiaojun Zhao, J. Christensen and 9 more. Science, 2007

4,374 citations recorded by the source corpus.

Subfields: Molecular Biology, Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/99e5b842aec9d42221a7b315f168a92d7bd58413

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Citations in the corpus

PI3K pathway alterations in cancer: variations on a theme (2008, neutral): “Finally, focal MET amplifications have been found in 22% of acquired gefitnib-resistant lung cancers and have been shown to restore AKT activity via MET-dependent phosphorylation of ERBB3 and consequent activation of PI3K (Engelman et al., 2007).”
Dynamic Reprogramming of the Kinome In Response to Targeted MEK Inhibition In Triple Negative Breast Cancer (2012, neutral): “HER3 upregulation was shown to play a major role in lapatinib resistance (Garrett, 2011) and in lung cancer MET amplification leads to gefitinib resistance (Engelman et al., 2007).”
HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. (2012, methodology): “Here, we used PC9/BRc1 cells that recapitulate the acquisition of resistance; they were clonally derived from drug-sensitive PC-9 cells (exon 19 deletion) and acquired a secondary T790M mutation by long-term passage in culture (14, 15).”
Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer (2018, neutral): “The most common bypass pathway is MET amplification, which accounts for 5–10% of cases with acquired resistance to EGFR TKIs [31, 32].”
Input–output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data (2009, result): “Moreover, it will undoubtedly prove interesting to compare our data-driven approach with recent theoretical work on network biology (Saez-Rodriguez et al, 2004; Del Vecchio et al, 2008 ).”
Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. (2008, background): “Engelman and colleagues reported that EGFR is linked to PI3K/Akt signaling via ErbB3 in NSCLC cell lines that are sensitive to EGFR tyrosine kinase inhibitors (31) and that MET amplification leads to gefitinib resistance by binding and activation of ErbB3 (12).”
The epidermal growth factor receptor family: Biology driving targeted therapeutics (2008, background): “MET is amplified in about 20 % of lung cancers with resistance to gefitinib or erlotinib, and is able to transactivate ErbB3 thereby promoting cell survival in gefitinib-resistant lung cancer cell lines [46].”