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

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Title: MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling.
Authors: Engelman, Jeffrey A., Zejnullahu, Kreshnik, Mitsudomi, Tetsuya, Youngchul Song, Hyland, Courtney, Park, Joon Oh, Lindeman, Neal, Gale, Christopher-Michael, Xiaojun Zhao, Christensen, James, Kosaka, Takayuki, Holmes, Alison J., Rogers, Andrew M., Cappuzzo, Federico, Mok, Tony, Lee, Charles, Johnson, Bruce E., Cantley, Lewis C., Jänne, Pasi A.
Source: Science (pre-March 2025). 5/18/2007, Vol. 316 Issue 5827, p1039-1043. 5p.
Subjects: Gene amplification, Lung cancer, Epidermal growth factor, Cancer cells, Cancer treatment, Proto-oncogenes, Drug resistance, Cellular pathology, Medical research
Abstract: The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene, inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) Lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
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  Data: MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling.
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  Data: <searchLink fieldCode="AR" term="%22Engelman%2C+Jeffrey+A%2E%22">Engelman, Jeffrey A.</searchLink><br /><searchLink fieldCode="AR" term="%22Zejnullahu%2C+Kreshnik%22">Zejnullahu, Kreshnik</searchLink><br /><searchLink fieldCode="AR" term="%22Mitsudomi%2C+Tetsuya%22">Mitsudomi, Tetsuya</searchLink><br /><searchLink fieldCode="AR" term="%22Youngchul+Song%22">Youngchul Song</searchLink><br /><searchLink fieldCode="AR" term="%22Hyland%2C+Courtney%22">Hyland, Courtney</searchLink><br /><searchLink fieldCode="AR" term="%22Park%2C+Joon+Oh%22">Park, Joon Oh</searchLink><br /><searchLink fieldCode="AR" term="%22Lindeman%2C+Neal%22">Lindeman, Neal</searchLink><br /><searchLink fieldCode="AR" term="%22Gale%2C+Christopher-Michael%22">Gale, Christopher-Michael</searchLink><br /><searchLink fieldCode="AR" term="%22Xiaojun+Zhao%22">Xiaojun Zhao</searchLink><br /><searchLink fieldCode="AR" term="%22Christensen%2C+James%22">Christensen, James</searchLink><br /><searchLink fieldCode="AR" term="%22Kosaka%2C+Takayuki%22">Kosaka, Takayuki</searchLink><br /><searchLink fieldCode="AR" term="%22Holmes%2C+Alison+J%2E%22">Holmes, Alison J.</searchLink><br /><searchLink fieldCode="AR" term="%22Rogers%2C+Andrew+M%2E%22">Rogers, Andrew M.</searchLink><br /><searchLink fieldCode="AR" term="%22Cappuzzo%2C+Federico%22">Cappuzzo, Federico</searchLink><br /><searchLink fieldCode="AR" term="%22Mok%2C+Tony%22">Mok, Tony</searchLink><br /><searchLink fieldCode="AR" term="%22Lee%2C+Charles%22">Lee, Charles</searchLink><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Bruce+E%2E%22">Johnson, Bruce E.</searchLink><br /><searchLink fieldCode="AR" term="%22Cantley%2C+Lewis+C%2E%22">Cantley, Lewis C.</searchLink><br /><searchLink fieldCode="AR" term="%22Jänne%2C+Pasi+A%2E%22">Jänne, Pasi A.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 5/18/2007, Vol. 316 Issue 5827, p1039-1043. 5p.
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  Data: <searchLink fieldCode="DE" term="%22Gene+amplification%22">Gene amplification</searchLink><br /><searchLink fieldCode="DE" term="%22Lung+cancer%22">Lung cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Epidermal+growth+factor%22">Epidermal growth factor</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+cells%22">Cancer cells</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+treatment%22">Cancer treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Proto-oncogenes%22">Proto-oncogenes</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance%22">Drug resistance</searchLink><br /><searchLink fieldCode="DE" term="%22Cellular+pathology%22">Cellular pathology</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+research%22">Medical research</searchLink>
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  Label: Abstract
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  Data: The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene, inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) Lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=25254770
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        Value: 10.1126/science.1141478
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        Text: English
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        PageCount: 5
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        Type: general
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      – SubjectFull: Epidermal growth factor
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