The novel selective pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro

Makoto Kawamoto; Keigo Ozono; Yasuhiro Oyama; Akio Yamasaki; Yoshinao Oda; Hideya Onishi

doi:10.21873/anticanres.12435

The novel selective pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro

Makoto Kawamoto, Keigo Ozono, Yasuhiro Oyama, Akio Yamasaki, Yoshinao Oda, Hideya Onishi

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

6 Citations (Scopus)

Abstract

We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ, TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC proliferation in TYGBK-1, and on invasive potential and vascular endothelial growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579 could be a promising treatment option for patients with GBC.

Original language	English
Pages (from-to)	1979-1986
Number of pages	8
Journal	Anticancer research
Volume	38
Issue number	4
DOIs	https://doi.org/10.21873/anticanres.12435
Publication status	Published - Apr 2018

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Oncology
Cancer Research

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10.21873/anticanres.12435

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title = "The novel selective pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro",

abstract = "We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ, TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC proliferation in TYGBK-1, and on invasive potential and vascular endothelial growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579 could be a promising treatment option for patients with GBC.",

author = "Makoto Kawamoto and Keigo Ozono and Yasuhiro Oyama and Akio Yamasaki and Yoshinao Oda and Hideya Onishi",

note = "Funding Information: This study was supported by the Japan Society for the Promotion of Science KAKENHI Grant Number 26462146 and 16K10603. Publisher Copyright: {\textcopyright} 2018 International Institute of Anticancer Research. All rights reserved.",

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AU - Kawamoto, Makoto

AU - Ozono, Keigo

AU - Oyama, Yasuhiro

AU - Yamasaki, Akio

AU - Oda, Yoshinao

AU - Onishi, Hideya

N1 - Funding Information: This study was supported by the Japan Society for the Promotion of Science KAKENHI Grant Number 26462146 and 16K10603. Publisher Copyright: © 2018 International Institute of Anticancer Research. All rights reserved.

PY - 2018/4

Y1 - 2018/4

N2 - We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ, TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC proliferation in TYGBK-1, and on invasive potential and vascular endothelial growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579 could be a promising treatment option for patients with GBC.

AB - We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors have been evaluated and their dramatic clinical activity is being shown for a variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO-7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ, TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC proliferation in TYGBK-1, and on invasive potential and vascular endothelial growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579 could be a promising treatment option for patients with GBC.

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The novel selective pan-TRK inhibitor ONO-7579 exhibits antitumor efficacy against human gallbladder cancer in vitro

Abstract

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