The Novel Selective Pan-TRK Inhibitor ONO-7579 Exhibits Antitumor Efficacy Against Human Gallbladder Cancer In Vitro.
The Novel Selective Pan-TRK Inhibitor ONO-7579 Exhibits Antitumor Efficacy Against Human Gallbladder Cancer In Vitro.
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DOI：
10.21873/anticanres.12435
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发表时间：
2018-04
影响因子：
2
通讯作者：
M. Kawamoto;K. Ozono;Yasuhiro Oyama;A. Yamasaki;Y. Oda;H. Onishi
中科院分区：
文献类型：
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作者：
M. Kawamoto;K. Ozono;Yasuhiro Oyama;A. Yamasaki;Y. Oda;H. Onishi
我们之前报道了脑源性神经营养因子(BDNF)/神经营养受体酪氨酸激酶2 （NTRK2/TRKB）信号传导有助于诱导胆囊癌（GBC）的恶性表型。最近，人们对泛trk抑制剂进行了评估，并在I期试验中显示了它们对多种含有NTRK重排的癌症类型的显著临床活性。ONO-7579是一种口服泛trk抑制剂，目前正在trk重排实体瘤的I/II期临床试验中进行研究。在这项研究中，我们用KRAS突变体NOZ， TYGBK-1或不含NOZ， TYGBK-1的GBC细胞来评估ONO-7579的抗癌作用。我们的研究表明ONO-7579对TYGBK-1中GBC的增殖有抑制作用，对TYGBK-1和NOZ中侵袭电位和血管内皮生长因子表达有抑制作用。我们的数据表明ONO-7579可能是GBC患者的一种有希望的治疗选择。
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.