FGFR1 expression levels predict BGJ398 Sensitivity of FGFR1-dependent head and neck Squamous cell cancers

Friederike Göke, Alina Franzen, Trista K. Hinz, Lindsay A. Marek, Petros Yoon, Rakesh Sharma, Maike Bode, Anne Von Maessenhausen, Brigitte Lankat-Buttgereit, Antonia Göke, Carsten Golletz, Robert Kirsten, Diana Boehm, Wenzel Vogel, Emily K. Kleczko, Justin R. Eagles, Fred R. Hirsch, Tobias Van Bremen, Friedrich Bootz, Andreas SchroeckJihye Kim, Aik-Choon Tan, Antonio Jimeno, Lynn E. Heasley, Sven Perner

Research output: Contribution to journalArticle

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Abstract

Purpose: FGFR1 copy-number gain (CNG) occurs in head and neck squamous cell cancers (HNSCC) and is used for patient selection in FGFR-specific inhibitor clinical trials. This study explores FGFR1 mRNA and protein levels in HNSCC cell lines, primary tumors, and patient-derived xenografts (PDX) as predictors of sensitivity to the FGFR inhibitor, NVP-BGJ398. Experimental Design: FGFR1 status, expression levels, and BGJ398 sensitive growth were measured in 12 HNSCC cell lines. Primary HNSCCs (n = 353) were assessed for FGFR1 CNG and mRNA levels, and HNSCC TCGA data were interrogated as an independent sample set. HNSCC PDXs (n = 39) were submitted to FGFR1 copy-number detection and mRNA assays to identify putative FGFR1-dependent tumors. Results: Cell line sensitivity to BGJ398 is associated with FGFR1 mRNA and protein levels, not FGFR1 CNG. Thirtyone percent of primary HNSCC tumors expressed FGFR1 mRNA, 18% exhibited FGFR1 CNG, 35% of amplified tumors were also positive for FGFR1 mRNA. This relationship was confirmed with the TCGA dataset. Using high FGFR1 mRNA for selection, 2 HNSCC PDXs were identified, one of which also exhibited FGFR1 CNG. The nonamplified tumor with high mRNA levels exhibited in vivo sensitivity to BGJ398. Conclusions: FGFR1 expression associates with BGJ398 sensitivity in HNSCC cell lines and predicts tyrosine kinase inhibitor sensitivity in PDXs. Our results support FGFR1 mRNA or protein expression, rather than FGFR1 CNG as a predictive biomarker for the response to FGFR inhibitors in a subset of patients suffering fromHNSCC.

Original languageEnglish
Pages (from-to)4356-4364
Number of pages9
JournalClinical Cancer Research
Volume21
Issue number19
DOIs
Publication statusPublished - 2015 Oct 1
Externally publishedYes

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Squamous Cell Neoplasms
Head and Neck Neoplasms
Head
Messenger RNA
Receptor, Fibroblast Growth Factor, Type 1
Cell Line
Neoplasms
3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-(4-(4-ethylpiperazin-1-yl)-phenylamino)pyrimidin-4-yl)-1-methylurea
Tumor Cell Line
Heterografts
Protein-Tyrosine Kinases
Patient Selection
Research Design
Biomarkers
Clinical Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Göke, F., Franzen, A., Hinz, T. K., Marek, L. A., Yoon, P., Sharma, R., ... Perner, S. (2015). FGFR1 expression levels predict BGJ398 Sensitivity of FGFR1-dependent head and neck Squamous cell cancers. Clinical Cancer Research, 21(19), 4356-4364. https://doi.org/10.1158/1078-0432.CCR-14-3357

FGFR1 expression levels predict BGJ398 Sensitivity of FGFR1-dependent head and neck Squamous cell cancers. / Göke, Friederike; Franzen, Alina; Hinz, Trista K.; Marek, Lindsay A.; Yoon, Petros; Sharma, Rakesh; Bode, Maike; Von Maessenhausen, Anne; Lankat-Buttgereit, Brigitte; Göke, Antonia; Golletz, Carsten; Kirsten, Robert; Boehm, Diana; Vogel, Wenzel; Kleczko, Emily K.; Eagles, Justin R.; Hirsch, Fred R.; Van Bremen, Tobias; Bootz, Friedrich; Schroeck, Andreas; Kim, Jihye; Tan, Aik-Choon; Jimeno, Antonio; Heasley, Lynn E.; Perner, Sven.

In: Clinical Cancer Research, Vol. 21, No. 19, 01.10.2015, p. 4356-4364.

Research output: Contribution to journalArticle

Göke, F, Franzen, A, Hinz, TK, Marek, LA, Yoon, P, Sharma, R, Bode, M, Von Maessenhausen, A, Lankat-Buttgereit, B, Göke, A, Golletz, C, Kirsten, R, Boehm, D, Vogel, W, Kleczko, EK, Eagles, JR, Hirsch, FR, Van Bremen, T, Bootz, F, Schroeck, A, Kim, J, Tan, A-C, Jimeno, A, Heasley, LE & Perner, S 2015, 'FGFR1 expression levels predict BGJ398 Sensitivity of FGFR1-dependent head and neck Squamous cell cancers', Clinical Cancer Research, vol. 21, no. 19, pp. 4356-4364. https://doi.org/10.1158/1078-0432.CCR-14-3357
Göke, Friederike ; Franzen, Alina ; Hinz, Trista K. ; Marek, Lindsay A. ; Yoon, Petros ; Sharma, Rakesh ; Bode, Maike ; Von Maessenhausen, Anne ; Lankat-Buttgereit, Brigitte ; Göke, Antonia ; Golletz, Carsten ; Kirsten, Robert ; Boehm, Diana ; Vogel, Wenzel ; Kleczko, Emily K. ; Eagles, Justin R. ; Hirsch, Fred R. ; Van Bremen, Tobias ; Bootz, Friedrich ; Schroeck, Andreas ; Kim, Jihye ; Tan, Aik-Choon ; Jimeno, Antonio ; Heasley, Lynn E. ; Perner, Sven. / FGFR1 expression levels predict BGJ398 Sensitivity of FGFR1-dependent head and neck Squamous cell cancers. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 19. pp. 4356-4364.
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abstract = "Purpose: FGFR1 copy-number gain (CNG) occurs in head and neck squamous cell cancers (HNSCC) and is used for patient selection in FGFR-specific inhibitor clinical trials. This study explores FGFR1 mRNA and protein levels in HNSCC cell lines, primary tumors, and patient-derived xenografts (PDX) as predictors of sensitivity to the FGFR inhibitor, NVP-BGJ398. Experimental Design: FGFR1 status, expression levels, and BGJ398 sensitive growth were measured in 12 HNSCC cell lines. Primary HNSCCs (n = 353) were assessed for FGFR1 CNG and mRNA levels, and HNSCC TCGA data were interrogated as an independent sample set. HNSCC PDXs (n = 39) were submitted to FGFR1 copy-number detection and mRNA assays to identify putative FGFR1-dependent tumors. Results: Cell line sensitivity to BGJ398 is associated with FGFR1 mRNA and protein levels, not FGFR1 CNG. Thirtyone percent of primary HNSCC tumors expressed FGFR1 mRNA, 18{\%} exhibited FGFR1 CNG, 35{\%} of amplified tumors were also positive for FGFR1 mRNA. This relationship was confirmed with the TCGA dataset. Using high FGFR1 mRNA for selection, 2 HNSCC PDXs were identified, one of which also exhibited FGFR1 CNG. The nonamplified tumor with high mRNA levels exhibited in vivo sensitivity to BGJ398. Conclusions: FGFR1 expression associates with BGJ398 sensitivity in HNSCC cell lines and predicts tyrosine kinase inhibitor sensitivity in PDXs. Our results support FGFR1 mRNA or protein expression, rather than FGFR1 CNG as a predictive biomarker for the response to FGFR inhibitors in a subset of patients suffering fromHNSCC.",
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T1 - FGFR1 expression levels predict BGJ398 Sensitivity of FGFR1-dependent head and neck Squamous cell cancers

AU - Göke, Friederike

AU - Franzen, Alina

AU - Hinz, Trista K.

AU - Marek, Lindsay A.

AU - Yoon, Petros

AU - Sharma, Rakesh

AU - Bode, Maike

AU - Von Maessenhausen, Anne

AU - Lankat-Buttgereit, Brigitte

AU - Göke, Antonia

AU - Golletz, Carsten

AU - Kirsten, Robert

AU - Boehm, Diana

AU - Vogel, Wenzel

AU - Kleczko, Emily K.

AU - Eagles, Justin R.

AU - Hirsch, Fred R.

AU - Van Bremen, Tobias

AU - Bootz, Friedrich

AU - Schroeck, Andreas

AU - Kim, Jihye

AU - Tan, Aik-Choon

AU - Jimeno, Antonio

AU - Heasley, Lynn E.

AU - Perner, Sven

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Purpose: FGFR1 copy-number gain (CNG) occurs in head and neck squamous cell cancers (HNSCC) and is used for patient selection in FGFR-specific inhibitor clinical trials. This study explores FGFR1 mRNA and protein levels in HNSCC cell lines, primary tumors, and patient-derived xenografts (PDX) as predictors of sensitivity to the FGFR inhibitor, NVP-BGJ398. Experimental Design: FGFR1 status, expression levels, and BGJ398 sensitive growth were measured in 12 HNSCC cell lines. Primary HNSCCs (n = 353) were assessed for FGFR1 CNG and mRNA levels, and HNSCC TCGA data were interrogated as an independent sample set. HNSCC PDXs (n = 39) were submitted to FGFR1 copy-number detection and mRNA assays to identify putative FGFR1-dependent tumors. Results: Cell line sensitivity to BGJ398 is associated with FGFR1 mRNA and protein levels, not FGFR1 CNG. Thirtyone percent of primary HNSCC tumors expressed FGFR1 mRNA, 18% exhibited FGFR1 CNG, 35% of amplified tumors were also positive for FGFR1 mRNA. This relationship was confirmed with the TCGA dataset. Using high FGFR1 mRNA for selection, 2 HNSCC PDXs were identified, one of which also exhibited FGFR1 CNG. The nonamplified tumor with high mRNA levels exhibited in vivo sensitivity to BGJ398. Conclusions: FGFR1 expression associates with BGJ398 sensitivity in HNSCC cell lines and predicts tyrosine kinase inhibitor sensitivity in PDXs. Our results support FGFR1 mRNA or protein expression, rather than FGFR1 CNG as a predictive biomarker for the response to FGFR inhibitors in a subset of patients suffering fromHNSCC.

AB - Purpose: FGFR1 copy-number gain (CNG) occurs in head and neck squamous cell cancers (HNSCC) and is used for patient selection in FGFR-specific inhibitor clinical trials. This study explores FGFR1 mRNA and protein levels in HNSCC cell lines, primary tumors, and patient-derived xenografts (PDX) as predictors of sensitivity to the FGFR inhibitor, NVP-BGJ398. Experimental Design: FGFR1 status, expression levels, and BGJ398 sensitive growth were measured in 12 HNSCC cell lines. Primary HNSCCs (n = 353) were assessed for FGFR1 CNG and mRNA levels, and HNSCC TCGA data were interrogated as an independent sample set. HNSCC PDXs (n = 39) were submitted to FGFR1 copy-number detection and mRNA assays to identify putative FGFR1-dependent tumors. Results: Cell line sensitivity to BGJ398 is associated with FGFR1 mRNA and protein levels, not FGFR1 CNG. Thirtyone percent of primary HNSCC tumors expressed FGFR1 mRNA, 18% exhibited FGFR1 CNG, 35% of amplified tumors were also positive for FGFR1 mRNA. This relationship was confirmed with the TCGA dataset. Using high FGFR1 mRNA for selection, 2 HNSCC PDXs were identified, one of which also exhibited FGFR1 CNG. The nonamplified tumor with high mRNA levels exhibited in vivo sensitivity to BGJ398. Conclusions: FGFR1 expression associates with BGJ398 sensitivity in HNSCC cell lines and predicts tyrosine kinase inhibitor sensitivity in PDXs. Our results support FGFR1 mRNA or protein expression, rather than FGFR1 CNG as a predictive biomarker for the response to FGFR inhibitors in a subset of patients suffering fromHNSCC.

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