2. Academic Validation
  3. E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical Models

E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical Models

  • Mol Cancer Ther. 2016 Nov;15(11):2630-2639. doi: 10.1158/1535-7163.MCT-16-0261.
Saori Watanabe Miyano 1 2,  Yuji Yamamoto 1,  Kotaro Kodama 1,  Yukiko Miyajima 1,  Masaki Mikamoto 1,  Takayuki Nakagawa 1,  Hiroko Kuramochi 1,  Setsuo Funasaka 1,  Satoshi Nagao 1,  Naoko Hata Sugi 1,  Kiyoshi Okamoto 1,  Yukinori Minoshima 1,  Yusuke Nakatani 1,  Yuki Karoji 1,  Isao Ohashi 1,  Yoshinobu Yamane 1,  Toshimi Okada 1,  Tomohiro Matsushima 1,  Junji Matsui 1,  Masao Iwata 1,  Toshimitsu Uenaka 1,  Akihiko Tsuruoka 3
Affiliations

Affiliations

  • 1 Tsukuba Research Laboratories, Eisai Co., Ltd, Tsukuba-shi, Ibaraki, Japan.
  • 2 Department of Genomics-Based Drug Discovery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
  • 3 Tsukuba Research Laboratories, Eisai Co., Ltd, Tsukuba-shi, Ibaraki, Japan. a-tsuruoka@hhc.eisai.co.jp.
PMID: 27535969 DOI: 10.1158/1535-7163.MCT-16-0261
Abstract

The FGFR signaling pathway has a crucial role in proliferation, survival, and migration of Cancer cells, tumor angiogenesis, and drug resistance. FGFR genetic abnormalities, such as gene fusion, mutation, and amplification, have been implicated in several types of Cancer. Therefore, FGFRs are considered potential targets for Cancer therapy. E7090 is an orally available and selective inhibitor of the tyrosine kinase activities of FGFR1, -2, and -3. In kinetic analyses of the interaction between E7090 and FGFR1 tyrosine kinase, E7090 associated more rapidly with FGFR1 than did the type II FGFR1 Inhibitor ponatinib, and E7090 dissociated more slowly from FGFR1, with a relatively longer residence time, than did the type I FGFR1 Inhibitor AZD4547, suggesting that its kinetics are more similar to the type V inhibitors, such as lenvatinib. E7090 showed selective antiproliferative activity against Cancer cell lines harboring FGFR genetic abnormalities and decreased tumor size in a mouse xenograft model using cell lines with dysregulated FGFR Furthermore, E7090 administration significantly prolonged the survival of mice with metastasized tumors in the lung. Our results suggest that E7090 is a promising candidate as a therapeutic agent for the treatment of tumors harboring FGFR genetic abnormalities. It is currently being investigated in a phase I clinical trial. Mol Cancer Ther; 15(11); 2630-9. ©2016 AACR.

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