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 Sou; Shuta Tomida; Masaomi Yamane; Masakiyo Sakaguchi; Shinichi Toyooka

doi:10.21873/anticanres.14237

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 Sou, Shuta Tomida, Masaomi Yamane, Masakiyo Sakaguchi, Shinichi Toyooka

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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 language	English
Pages (from-to)	2667-2673
Number of pages	7
Journal	Anticancer research
Volume	40
Issue number	5
DOIs	https://doi.org/10.21873/anticanres.14237
Publication status	Published - May 2020

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.14237

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Miyauchi, S., Shien, K., Takeda, T., Araki, K., Nakata, K., Miura, A., Takahashi, Y., Kurihara, E., Ogoshi, Y., Namba, K., Suzawa, K., Yamamoto, H., Okazaki, M., Sou, J., Tomida, S., Yamane, M., Sakaguchi, M., & Toyooka, S. (2020). Antitumor effects of pan-raf inhibitor LY3009120 against lung cancer cells harboring oncogenic BRAF mutation. Anticancer research, 40(5), 2667-2673. https://doi.org/10.21873/anticanres.14237

Miyauchi, S, Shien, K, Takeda, T, Araki, K, Nakata, K, Miura, A, Takahashi, Y, Kurihara, E, Ogoshi, Y, Namba, K, Suzawa, K , Yamamoto, H , Okazaki, M, Sou, J, Tomida, S, Yamane, M, Sakaguchi, M & Toyooka, S 2020, 'Antitumor effects of pan-raf inhibitor LY3009120 against lung cancer cells harboring oncogenic BRAF mutation', Anticancer research, vol. 40, no. 5, pp. 2667-2673. https://doi.org/10.21873/anticanres.14237

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

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.",

keywords = "BRAF mutation, LY3009120, Non-small cell lung cancer, Pan-RAF inhibitor",

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

year = "2020",

month = may,

doi = "10.21873/anticanres.14237",

language = "English",

volume = "40",

pages = "2667--2673",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

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TY - JOUR

T1 - Antitumor effects of pan-raf inhibitor LY3009120 against lung cancer cells harboring oncogenic BRAF mutation

AU - Miyauchi, Shunsaku

AU - Shien, Kazuhiko

AU - Takeda, Tatsuaki

AU - Araki, Kota

AU - Nakata, Kentaro

AU - Miura, Akihiro

AU - Takahashi, Yuta

AU - Kurihara, Eisuke

AU - Ogoshi, Yusuke

AU - Namba, Kei

AU - Suzawa, Ken

AU - Yamamoto, Hiromasa

AU - Okazaki, Mikio

AU - Sou, Junichi

AU - Tomida, Shuta

AU - Yamane, Masaomi

AU - Sakaguchi, Masakiyo

AU - Toyooka, Shinichi

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - BRAF mutation

KW - LY3009120

KW - Non-small cell lung cancer

KW - Pan-RAF inhibitor

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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