Antitumor effects of pan-raf inhibitor LY3009120 against lung cancer cells harboring oncogenic BRAF mutation

Shunsaku Miyauchi, Kazuhiko Shien, Tatsuaki Takeda, Kota Araki, Kentaro Nakata, Akihiro Miura, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Kei Namba, Ken Suzawa, Hiromasa Yamamoto, Mikio Okazaki, Junichi Soh, Shuta Tomida, Masaomi Yamane, Masakiyo Sakaguchi, Shinichi Toyooka

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aim: The therapeutic strategy for patients with non-small-cell lung cancer (NSCLC) harboring the BRAF non-V600E mutation has not been established. LY3009120, a newly discovered pan-RAF inhibitor, has shown strong antitumor effects in cancers with various BRAF genotypes. This study investigated the antitumor effects of LY3009120 in NSCLC cells harboring the BRAF non-V600E mutation. Materials and Methods: We examined the antitumor effects of LY3009120 by MTS assay and flow cytometry. We analyzed the expression status of proteins by western blot. The mouse xenograft models were used for the in vivo experiments. Results: LY3009120 suppressed BRAFrelated downstream pathway molecules and induced cleavage of poly ADP-ribose polymerase in all examined NSCLC cell lines. LY3009120 also inhibited in vivo tumor growth in NSCLC cells harboring the BRAF non-V600E mutation. Conclusion: LY3009120 is a potent therapeutic agent for patients with BRAF non-V600E mutant NSCLC.

Original languageEnglish
Pages (from-to)2667-2673
Number of pages7
JournalAnticancer research
Volume40
Issue number5
DOIs
Publication statusPublished - May 2020

Keywords

  • BRAF mutation
  • LY3009120
  • Non-small cell lung cancer
  • Pan-RAF inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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