AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling
Most tumors develop resistance to targeted cancer drugs, even though these drugs have produced substantial clinical responses. Here we established anaplastic lymphoma kinase (ALK)‐positive drug‐resistant lung cancer cell lines, which are resistant to ceritinib (LDK378). We found that ceritinib treat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-04-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.12162 |
| _version_ | 1811220753967742976 |
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| author | Yi Zhao Yi Yang Yunhua Xu Shun Lu Hong Jian |
| author_facet | Yi Zhao Yi Yang Yunhua Xu Shun Lu Hong Jian |
| author_sort | Yi Zhao |
| collection | DOAJ |
| description | Most tumors develop resistance to targeted cancer drugs, even though these drugs have produced substantial clinical responses. Here we established anaplastic lymphoma kinase (ALK)‐positive drug‐resistant lung cancer cell lines, which are resistant to ceritinib (LDK378). We found that ceritinib treatment resulted in robust upregulation of SRC activity, as measured by the phosphorylation of the SRC substrate paxillin. Knockdown of SRC alone with siRNA effectively sensitized ceritinib resistance in ALK‐positive cells. Furthermore, SRC inhibition by AZD0530 was effective in ALK‐resistant cancer cells. Thus, ALK inhibition by ceritinib may lead to upregulation of SRC signaling, and AZD0530 could serve as a potential drug in the clinic to treat ALK‐resistant lung cancer patients. |
| first_indexed | 2024-04-12T07:46:49Z |
| format | Article |
| id | doaj.art-937089473c1a4810a3586d92807b766a |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-12T07:46:49Z |
| publishDate | 2017-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-937089473c1a4810a3586d92807b766a2022-12-22T03:41:41ZengWileyFEBS Open Bio2211-54632017-04-017447247610.1002/2211-5463.12162AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signalingYi Zhao0Yi Yang1Yunhua Xu2Shun Lu3Hong Jian4Shanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University ChinaShanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University ChinaShanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University ChinaShanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University ChinaShanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University ChinaMost tumors develop resistance to targeted cancer drugs, even though these drugs have produced substantial clinical responses. Here we established anaplastic lymphoma kinase (ALK)‐positive drug‐resistant lung cancer cell lines, which are resistant to ceritinib (LDK378). We found that ceritinib treatment resulted in robust upregulation of SRC activity, as measured by the phosphorylation of the SRC substrate paxillin. Knockdown of SRC alone with siRNA effectively sensitized ceritinib resistance in ALK‐positive cells. Furthermore, SRC inhibition by AZD0530 was effective in ALK‐resistant cancer cells. Thus, ALK inhibition by ceritinib may lead to upregulation of SRC signaling, and AZD0530 could serve as a potential drug in the clinic to treat ALK‐resistant lung cancer patients.https://doi.org/10.1002/2211-5463.12162ALKAZD0530NSCLCresistanceSRC |
| spellingShingle | Yi Zhao Yi Yang Yunhua Xu Shun Lu Hong Jian AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling FEBS Open Bio ALK AZD0530 NSCLC resistance SRC |
| title | AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling |
| title_full | AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling |
| title_fullStr | AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling |
| title_full_unstemmed | AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling |
| title_short | AZD0530 sensitizes drug‐resistant ALK‐positive lung cancer cells by inhibiting SRC signaling |
| title_sort | azd0530 sensitizes drug resistant alk positive lung cancer cells by inhibiting src signaling |
| topic | ALK AZD0530 NSCLC resistance SRC |
| url | https://doi.org/10.1002/2211-5463.12162 |
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