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