PMID- 29599313 OWN - NLM STAT- MEDLINE DCOM- 20180509 LR - 20180816 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 38 IP - 4 DP - 2018 Apr TI - The Novel Selective Pan-TRK Inhibitor ONO-7579 Exhibits Antitumor Efficacy Against Human Gallbladder Cancer In Vitro. PG - 1979-1986 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. CI - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Kawamoto, Makoto AU - Kawamoto M AD - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. AD - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Ozono, Keigo AU - Ozono K AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Oyama, Yasuhiro AU - Oyama Y AD - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. AD - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Yamasaki, Akio AU - Yamasaki A AD - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. AD - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Oda, Yoshinao AU - Oda Y AD - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Onishi, Hideya AU - Onishi H AD - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ohnishi@surg1.med.kyushu-u.ac.jp. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (ONO-7579) RN - 0 (Organic Chemicals) RN - 0 (Protein Kinase Inhibitors) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 7171WSG8A2 (BDNF protein, human) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) SB - IM MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Epithelial-Mesenchymal Transition/drug effects MH - Gallbladder Neoplasms/*drug therapy/enzymology/metabolism/pathology MH - Humans MH - Membrane Glycoproteins/*antagonists & inhibitors/biosynthesis MH - Neoplasm Invasiveness MH - Organic Chemicals/chemistry/*pharmacology MH - Protein Kinase Inhibitors/*pharmacology MH - Receptor, trkB/*antagonists & inhibitors/biosynthesis MH - Vascular Endothelial Growth Factor A/biosynthesis OTO - NOTNLM OT - ONO-7579 OT - TRK inhibitor OT - TRKB OT - gallbladder cancer EDAT- 2018/03/31 06:00 MHDA- 2018/05/10 06:00 CRDT- 2018/03/31 06:00 PHST- 2018/01/19 00:00 [received] PHST- 2018/02/16 00:00 [revised] PHST- 2018/02/26 00:00 [accepted] PHST- 2018/03/31 06:00 [entrez] PHST- 2018/03/31 06:00 [pubmed] PHST- 2018/05/10 06:00 [medline] AID - 38/4/1979 [pii] AID - 10.21873/anticanres.12435 [doi] PST - ppublish SO - Anticancer Res. 2018 Apr;38(4):1979-1986. doi: 10.21873/anticanres.12435.