Tyrosine kinase inhibitors bind and inhibit overexpressed FGFR1 dimers

Stable Identifier
Reaction [binding]
Homo sapiens
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Treatment of FGFR1-amplified lung and breast cancer cell lines with the in vitro reagents PD173704, SU5402 and FIIN-1 inhibits proliferation, while cells expressing wild-type levels of FGFR1 are insensitive to inhibitors, suggesting that amplified FGFR1 may be a suitable therapeutic target in some cancer lines (Weiss, 2010; Reis-Filho, 2006; Dutt, 2011; Turner, 2010). In fact, a number of other small molecule inhibitors, including Dovitinib and AZD4547, are currently in clinical trials for treatment of FGFR1-amplified cancers (reviewed in Turner and Grose, 2010; Wesche, 2011; http://ClinicalTrials.gov)
Literature References
PubMed ID Title Journal Year
21711248 Fibroblast growth factors and their receptors in cancer

Haglund, K, Wesche, J, Haugsten, EM

Biochem J 2011
20179196 FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer

Marchio, C, Ashworth, A, Reis-Filho, JS, Lambros, M, Iorns, E, Gillett, C, Geyer, F, Natrajan, R, Sharpe, R, Lopez-Garcia, MA, Turner, N, Tutt, A, Grigoriadis, A, Mackay, A, Pearson, A

Cancer Res 2010
17121884 FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas

Sarrio, D, Hardisson, D, Savage, K, Weber, B, Schmitt, FC, Ashworth, A, Lambros, MB, Reis-Filho, JS, Dexter, T, Iravani, M, Turner, NC, Jones, C, Fenwick, K, Grigoriadis, A, Lakhani, SR, Palacios, J, Simpson, PT, Mackay, A

Clin Cancer Res 2006
21160078 Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer

Sietsma, H, Smit, E, Solomon, B, Sollberg, S, Soltermann, A, Sos, ML, Stoelben, E, Thomas, RK, Sänger, J, Timens, W, Thunnissen, E, Wagener, P, Cappuzzo, F, Buettner, R, Brustugun, OT, Brambilla, E, Brambilla, C, Baumann, M, Beroukhim, R, Baessmann, I, Balke-Want, H, Ansén, S, Altmüller, J, Zander, T, Wright, G, Leenders, F, Koker, M, Heynck, S, Klebl, B, Heukamp, LC, Heuckmann, JM, Hallek, M, Heideman, D, Groen, H, Fischer, F, Gabler, F, Ernestus, K, Engel-Riedel, W, Damiani, S, Conron, M, Dabow, I, Clement, J, Seidel, D, Schöttle, J, Russell, P, Rauh, D, Petersen, I, Querings, S, Perner, S, Nürnberg, P, Peifer, M, Moch, H, Menon, R, Ludwig, C, Maier, S, Ligorio, C, Lorimier, P, Wolf, J, Pao, W, Weiss, J, Wainer, Z, Ullrich, RT

Sci Transl Med 2010
20094046 Fibroblast growth factor signalling: from development to cancer

Grose, RP, Turner, N

Nat Rev Cancer 2010
21666749 Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Mermel, C, Hammerman, PS, Greulich, H, Gray, NS, Ramos, AH, Cho, J, Chande, A, Dutt, A, Tanaka, KE, Stransky, N, Meyerson, M, Sharifnia, T

PLoS One 2011
Functional status

Gain of function of Overexpressed FGFR1 homodimers [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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