Reference Detail

Ref Type

Journal Article

PMID

(27535969)

Authors

Watanabe Miyano S, Yamamoto Y, Kodama K, Miyajima Y, Mikamoto M, Nakagawa T, Kuramochi H, Funasaka S, Nagao S, Sugi NH, Okamoto K, Minoshima Y, Nakatani Y, Karoji Y, Ohashi I, Yamane Y, Okada T, Matsushima T, Matsui J, Iwata M, Uenaka T, Tsuruoka A

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Molecular cancer therapeutics	15	11	2016 Nov	2630-2639	Mol Cancer Ther

URL

Abstract Text

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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
E7090	E7090	88	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
E7090		E-7090\|Tasurgratinib	FGFR1 Inhibitor 28 FGFR2 Inhibitor 23 FGFR3 Inhibitor 19	E7090 is a selective inhibitor of FGFR1, FGFR2, and FGFR3, which may result in inhibition of cell proliferation and antitumor activity (PMID: 27535969).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FGFR1 amp	lung non-small cell carcinoma	sensitive	E7090	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a non-small cell lung cancer cell line, harboring FGFR1 amplification, treated with E7090 demonstrated decreased cell viability in culture and antitumor activity in xenograft models (PMID: 27535969).	27535969
FGFR3 Y373C	multiple myeloma	sensitive	E7090	Preclinical - Cell culture	Actionable	In a preclinical study, a multiple myeloma cell line harboring FGFR3 Y373C (PMID: 19901323) demonstrated sensitivity to E7090 in culture, resulting in decreased cell viability (PMID: 27535969).	19901323 27535969
FGFR2 amp	stomach cancer	sensitive	E7090	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a gastric cancer cell line harboring FGFR2 amplification demonstrated decreased cell viability in culture and antitumor activity in xenograft models when treated with E7090 (PMID: 27535969).	27535969
FGFR1 amp	estrogen-receptor positive breast cancer	sensitive	E7090	Preclinical - Cell culture	Actionable	In a preclinical study, an estrogen-receptor positive breast cancer cell line harboring FGFR1 amplification (PMID: 7506125) demonstrated sensitivity to E7090 in culture, resulting in decreased cell viability (PMID: 27535969).	7506125 27535969
FGFR1 amp	lung small cell carcinoma	sensitive	E7090	Preclinical - Cell culture	Actionable	In a preclinical study, a small cell lung cancer cell line harboring FGFR1 amplification demonstrated sensitivity to E7090, resulting in decreased cell viability in culture and antitumor activity in xenograft models (PMID: 27535969).	27535969
FGFR1 amp FGFR2 amp	breast cancer	sensitive	E7090	Preclinical - Cell line xenograft	Actionable	In a preclinical study, a breast cancer cell line, harboring FGFR1 amplification and FGFR2 amplification, treated with E7090 demonstrated decreased cell viability in culture and antitumor activity in xenograft models (PMID: 27535969).	27535969
FGFR2 pos FGFR3 pos	breast carcinoma	sensitive	E7090	Preclinical	Actionable	In a preclinical study, a mouse breast carcinoma cell line xenograft model demonstrated inhibition of tumor growth when treated with E7090, a result of decreased FGFR2 and FGFR3 activity (PMID: 27535969).	27535969
FGFR2 S252W	endometrial cancer	sensitive	E7090	Preclinical - Cell culture	Actionable	In a preclinical study, an endometrial cancer cell line harboring FGFR2 S252W (PMID: 18552176) demonstrated sensitivity to E7090 in culture, resulting in decreased cell viability (PMID: 27535969).	18552176 27535969