Reference Detail

Ref Type

Journal Article

PMID

(26036639)

Authors

Kunstlinger H, Fassunke J, Schildhaus HU, Brors B, Heydt C, Ihle MA, Mechtersheimer G, Wardelmann E, Buttner R, Merkelbach-Bruse S

Title

FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Oncotarget	6	24	2015 Aug 21	20215-30	Oncotarget

URL

Abstract Text

Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors.

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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

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

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
FGFR2 amp	myxoid liposarcoma	sensitive	Dovitinib	Preclinical	Actionable	In a preclinical study, Dovitinib (TKI258) increased apoptosis, inhibited cell proliferation and migration of myxoid liposarcoma cell lines harbors FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	myxoid liposarcoma	sensitive	PD173074	Preclinical	Actionable	In a preclinical study, PD173074 increased apoptosis, inhibited cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	myxoid liposarcoma	sensitive	Infigratinib	Preclinical	Actionable	In a preclinical study, Truseltiq (infigratinib) increased apoptosis, and inhibited cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	myxoid liposarcoma	sensitive	Dovitinib + Trabectedin	Preclinical	Actionable	In a preclinical study, Dovitinib (TKI258) and Yondelis (trabectedin) worked synergistically to increase apoptosis, inhibit cell proliferation and migration of myxoid liposarcoma cell lines harbors FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	stomach cancer	sensitive	PD173074	Preclinical - Cell culture	Actionable	In a preclinical study, PD173074 inhibited proliferation of a gastric cancer cell line harboring FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	stomach cancer	sensitive	Infigratinib	Preclinical	Actionable	In a preclinical study, Truseltiq (infigratinib) inhibited proliferation of gastric cancer cell lines harboring FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	myxoid liposarcoma	sensitive	PD173074 + Trabectedin	Preclinical	Actionable	In a preclinical study, PD173074 and Yondelis (trabectedin) worked synergistically to increase apoptosis, inhibit cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639).	26036639
FGFR2 amp	myxoid liposarcoma	sensitive	Infigratinib + Trabectedin	Preclinical	Actionable	In a preclinical study, Truseltiq (infigratinib) and Yondelis (trabectedin) worked synergistically to increase apoptosis, inhibit cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639).	26036639