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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

CT-707 Overcomes Resistance of Crizotinib through Activating PDPK1- AKT1 Pathway by Targeting FAK

Author(s): Caixia Liang, Ningning Zhang, Qiaoyun Tan, Shuxia Liu, Rongrong Luo, Yanrong Wang, Yuankai Shi* and Xiaohong Han*

Volume 19 , Issue 8 , 2019

Page: [655 - 665] Pages: 11

DOI: 10.2174/1568009618666181031152140

Price: $65


Background: Crizotinib established the position of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI) in the treatment of non-small cell lung cancer (NSCLC) while the therapy- resistance hindered those patients from benefitting continuously from the treatment. CT-707 is an inhibitor of ALK/focal adhesion kinase (FAK) and IGFR-1. H2228CR (crizotinib resistance, CR) and H3122CR NSCLC cell lines were generated from the parental cell line H2228 (EML4-ALK, E6a/b:A20, variant 3) and H3122(EML4-ALK, E13:A20, variant 1), respectively.

Methods: We investigated the antitumor effects CT-707 exerted against H3122CR in vitro /vivo.

Results: Importantly, our study provided evidence that CT-707 overcomes resistance to crizotinib through activating PDPK1-AKT1 pathway by targeting FAK. Meanwhile, by using an in-vivo H3122CR xenograft model, we found CT-707 inhibited tumor growth significantly without obvious side effects.

Conclusion: These findings indicate that CT-707 may be a promising therapeutic agent against crizotinib- resistance in NSCLC.

Keywords: Anaplastic lymphoma kinase, CT-707, crizotinib resistance, non-small cell lung cancer, xenograft model, therapeutic agent.

Graphical Abstract
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