The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations
Open accessPublished version of a preprint
Abstract
Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. However, 25% to 30% of patients with EGFR-activating mutations show intrinsic resistance, and the responders invariably acquire resistance to gefitinib. Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR-activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. Strong immunoreactivity for HGF in cancer cells was detected in lung adenocarcinoma patients harboring EGFR-activating mutations, but no T790M mutation or MET amplification, who showed intrinsic or acquired resistance to gefitinib. The findings indicate that HGF-mediated MET activation is a novel mechanism of gefitinib resistance in lung adenocarcinoma with EGFR-activating mutations. Therefore, inhibition of HGF-MET signaling may be a considerable strategy for more successful treatment with gefitinib.
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“Activation of MET by its ligand hepatic growth factor (HGF) was also sufficient to promote resistance through activation of downstream signaling (Yano et al., 2008).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Yano et al., 2008
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EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
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Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer
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MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
Self-citationEGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
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ERBB receptors and cancer: the complexity of targeted inhibitors
Hynes, N. E., & Lane, H. A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1609 · Cited by 3,379
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Self-citationMet, metastasis, motility and more
Birchmeier, C., Birchmeier, W., Gherardi, E., & Woude, G. F. V. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1261 · Cited by 2,652
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Metadata
- Authors
- Yano, S., Wang, W., Li, Q., Matsumoto, K., Sakurama, H., Nakamura, T., Ogino, H., Kakiuchi, S., Hanibuchi, M., Nishioka, Y., Uehara, H., Mitsudomi, T., Yatabe, Y., Nakamura, T., & Sone, S.
- Affiliations
- 1Medical Oncology and Divisions of
- Kanazawa University (JP)
- 3Respiratory Medicine and Rheumatology and
- Tokushima University (JP)
- 5Thoracic Surgery and
- Aichi Cancer Center Hospital (JP)
- ORCID
- Venue
- Cancer Research
- Published
- 2008-11-14
- Volume
- 68
- Issue
- 22
- Pages
- 9479-9487
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2119351872
- Cited by
- 643
- References
- 39
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 11 · 2023: 29 · 2022: 12 · 2021: 33 · 2020: 22 · 2019: 23 · 2018: 43 · 2017: 47 · 2016: 38 · 2015: 52 · 2014: 67 · 2013: 71 · 2012: 58
- FWCI
- 33.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- hepatocyte growth factor, gefitinib resistance, lung adenocarcinoma, EGFR activating mutations, phosphatidylinositol 3-kinase/Akt signaling, EGFR tyrosine kinase inhibitors, HGF/MET signaling, T790M mutation, MET amplification
- MeSH terms
- Gefitinib, Adenocarcinoma, Humans, Lung Neoplasms, Mutation, Phosphorylation, Proto-Oncogene Proteins, Quinazolines, Hepatocyte Growth Factor, Receptors, Growth Factor, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Phosphatidylinositol 3-Kinases, Receptor, ErbB-3, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, ErbB Receptors
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