Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance.

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Kodama T, Tsukaguchi T, Yoshida M, Kondoh O, Sakamoto H

Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance.

Cancer Lett. 2014 Sep 1;351(2):215-21. doi: 10.1016/j.canlet.2014.05.020. Epub 2014 Jun 2.

PubMed ID
24887559 [ View in PubMed
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Abstract

The clinical efficacy of the ALK inhibitor crizotinib has been demonstrated in ALK fusion-positive NSCLC; however, resistance to crizotinib certainly occurs through ALK secondary mutations in clinical use. Here we examined the efficacy of a selective ALK inhibitor alectinib/CH5424802 in models of crizotinib resistance. Alectinib led to tumor size reduction in EML4-ALK-positive xenograft tumors that failed to regress fully during the treatment with crizotinib. In addition, alectinib inhibited the growth of some EML4-ALK mutant-driven tumors, including the G1269A model. These results demonstrated that alectinib might provide therapeutic opportunities for crizotinib-treated patients with ALK secondary mutations.

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