116P Real-world and in silico incidence of fibroblast growth factor receptor (FGFR) 1-4 molecular alterations across multiple cancer types

Abstract Objective: Fibroblast growth factor receptor (FGFR) 2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

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Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

10.21203/rs.2.24557/v3 ◽

2020 ◽

Author(s):

Matthias Haase ◽

Anne Thiel ◽

Ute I. Scholl ◽

Hany Ashmawy ◽

Matthias Schott ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Adrenocortical Carcinoma ◽

Fibroblast Growth Factor Receptor ◽

Growth Factor Receptor ◽

Cell Types ◽

Beta Catenin ◽

Fibroblast Growth ◽

Mutational Status ◽

Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR)2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

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Design, Synthesis and Biological Evaluation of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-Substituted-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors

10.20944/preprints201609.0122.v1 ◽

2016 ◽

Author(s):

Zhen Zhang ◽

Dongmei Zhao ◽

Yang Dai ◽

Maosheng Cheng ◽

Meiyu Geng ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor Receptor ◽

Growth Factor Receptor ◽

Biological Evaluation ◽

Fibroblast Growth ◽

Design Synthesis ◽

Promising Target ◽

Cancer Types ◽

Synthesis And Biological Evaluation

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

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Subcellular localization of fibroblast growth factor receptor type 2 and correlation with CTNNB1 genotype in adrenocortical carcinoma

10.21203/rs.2.24557/v1 ◽

2020 ◽

Author(s):

Matthias Haase ◽

Anne Thiel ◽

Ute I. Scholl ◽

Hany Ashmawy ◽

Matthias Schott ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Adrenocortical Carcinoma ◽

Fibroblast Growth Factor Receptor ◽

Growth Factor Receptor ◽

Cell Types ◽

Beta Catenin ◽

Fibroblast Growth ◽

Mutational Status ◽

Cancer Types

Abstract Objective: Fibroblast growth factor receptor (FGFR)2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT) / beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types.

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Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience

British Journal of Cancer ◽

10.1038/s41416-021-01488-6 ◽

2021 ◽

Author(s):

Tracy L. Rose ◽

William H. Weir ◽

Gregory M. Mayhew ◽

Yoichiro Shibata ◽

Patrick Eulitt ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Real World ◽

Urothelial Cancer ◽

Fibroblast Growth Factor Receptor ◽

Growth Factor Receptor ◽

Fibroblast Growth ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition ◽

Metastatic Urothelial Cancer

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STUDI IN SILICO: PREDIKSI PENGARUH MUTASI TITIK GEN VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) TERHADAP STRUKTUR SEKUNDER PROTEIN

AL-Kauniyah Jurnal Biologi ◽

10.15408/kauniyah.v12i2.11804 ◽

2019 ◽

Vol 12 (2) ◽

pp. 220-228

Author(s):

Karina Karina ◽

Imam Rosadi ◽

Iis Rosliana ◽

Komang A. Wahyuningsih

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

In Silico ◽

Fibroblast Growth Factor Receptor ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Fibroblast Growth ◽

Endothelial Growth Factor

Angiogenesis merupakan proses penting untuk pertumbuhan dan regenerasi sel. Salah satu protein yang berperan dalam angiogenesis adalah vascular endothelial growth factor (VEGF). VEGF akan berinteraksi dengan reseptornya seperti vascular endothelial growth factor receptor-2 (VEGFR2) untuk meregulasi proses angiogenesis. Mutasi pada gen VEGFR2 pada manusia dilaporkan dapat menyebabkan penyakit strawberry mark (hemangioma). Oleh karena itu, perlu dilakukan studi dan penelusuran terkait mutasi yang berperan dalam terbentuknya hemangioma. Beberapa tahapan yang dilakukan untuk menganalisis pengaruh mutasi tersebut diantaranya dengan melakukan penelusuran informasi dasar dan komposisi gen VEGFR2, analisis ortolog dan paralog gen VEGFR2, dan analisis struktur sekunder protein VEGFR2 manusia. Hasilnya menunjukkan bahwa mutasi VEGFR2 pada basa ke-3741 yaitu sitosin (C) menjadi timin (T) dilaporkan ditemukan pada jaringan tumor hemangioma. Perubahan basa ke-3741 sitosin menjadi timin mengakibatkan perubahan asam amino prolin menjadi serin yang dapat berdampak pada regulasi ekspresi VEGF. Ortolog dan paralog dari gen VEGFR2 manusia adalah gen VEGFR2 mencit dan gen fibroblast growth factor receptor 1 (FGFR1) manusia. Hasil analisis pengaruh mutasi terhadap bentuk dan struktur protein menunjukkan tidak ada perubahan yang signifikan, namun posisi mutasi di bagian ekstraseluler sel diduga mempengaruhi regulasi ekspresi VEGF melalui ikatan ligan-reseptor.

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