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- W2235388618 abstract "Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAWe have shown that alectinib is a potent ALK inhibitor and is being evaluated in clinical trials for the treatment of ALK fusion-positive non-small cell lung cancer (NSCLC). Recently, RET and ROS1 fusion genes have been implicated as driver oncogenes in 1-2% of NSCLC and have been developed into promising molecular targets for antitumor agents. Here, we investigate the additional target indication of alectinib by testing its ability to inhibit the activity of RET and ROS1 kinases. In enzyme assay, alectinib showed kinase inhibitory activity against RET as wells as ALK but did not show against ROS1. Alectinib inhibited the growth of LC-2/ad cells harboring CCDC6-RET and Ba/F3 cells expressing KIF5B-RET by suppressing RET phosphorylation. Alectinib also showed antitumor activity in mouse models of RET fusion-positive tumors (LC-2/ad cells and Ba/F3 cells expressing KIF5B-RET) and of ALK fusion-positive tumors (NCI-H2228 cells harboring EML4-ALK). In addition, alectinib showed kinase inhibitory activity against RET gatekeeper mutations (RET V804L and V804M) and blocked KIF5B-RET gatekeeper mutation-driven cell growth. Our results suggest that alectinib is effective against RET fusion-positive tumors, as observed in ALK fusion-positive tumors. Thus, alectinib might be a therapeutic option for patients with RET fusion-positive NSCLC.Citation Format: Tatsushi Kodama, Toshiyuki Tsukaguchi, Yasuko Satoh, Miyuki Yoshida, Yoshiaki Watanabe, Osamu Kondoh, Hiroshi Sakamoto. Alectinib shows potent antitumor activity against both ALK- and RET-rearranged non-small cell lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 773. doi:10.1158/1538-7445.AM2015-773" @default.
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- W2235388618 date "2015-08-01" @default.
- W2235388618 modified "2023-09-26" @default.
- W2235388618 title "Abstract 773: Alectinib shows potent antitumor activity against both ALK- and RET-rearranged non-small cell lung cancers" @default.
- W2235388618 doi "https://doi.org/10.1158/1538-7445.am2015-773" @default.
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