title: AZD0530 sensitizes drug-resistant ALK-positive lung cancer cells by inhibiting SRC signaling.
abstract: 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.
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University China.
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.affiliation: Shanghai Lung Tumor Clinical Medical Center Shanghai Chest Hospital Shanghai Jiao Tong University China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jian
keywords: ALK; AZD0530; NSCLC; SRC; resistance