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Research Articles

FGFR Genetic Alterations Predict for Sensitivity to NVP-BGJ398, a Selective Pan-FGFR Inhibitor

Vito Guagnano, Audrey Kauffmann, Simon Wöhrle, Christelle Stamm, Moriko Ito, Louise Barys, Astrid Pornon, Yao Yao, Fang Li, Yun Zhang, Zhi Chen, Christopher J. Wilson, Vincent Bordas, Mickaël Le Douget, L. Alex Gaither, Jason Borawski, John E. Monahan, Kavitha Venkatesan, Thomas Brümmendorf, David M. Thomas, Carlos Garcia-Echeverria, Francesco Hofmann, William R. Sellers and Diana Graus-Porta
Vito Guagnano
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Audrey Kauffmann
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Simon Wöhrle
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Christelle Stamm
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Moriko Ito
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Louise Barys
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Astrid Pornon
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Yao Yao
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Fang Li
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Yun Zhang
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Zhi Chen
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Christopher J. Wilson
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Vincent Bordas
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Mickaël Le Douget
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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L. Alex Gaither
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Jason Borawski
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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John E. Monahan
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Kavitha Venkatesan
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Thomas Brümmendorf
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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David M. Thomas
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Carlos Garcia-Echeverria
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Francesco Hofmann
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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William R. Sellers
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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Diana Graus-Porta
1Global Discovery Chemistry, 2Disease Area Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Disease Area Oncology, 4Developmental and Molecular Pathways, and 5Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts; 6Developmental and Molecular Pathways, 7Oncology Translational Medicine, China Novartis Institutes for BioMedical Research, Shanghai, China; 8Sir Peter MacCallum Department of Oncology, University of Melbourne and Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, Australia
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DOI: 10.1158/2159-8290.CD-12-0210 Published December 2012
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    Figure 1.

    A, structure of NVP-BGJ398. B, the crystal structure of NVP-BGJ398 in complex with the tyrosine kinase domain of FGFR1 at 2.8 Å resolution. C, biochemical FGFR kinase assays; all assays were conducted with purified recombinant enzymes under optimized conditions using peptidic substrates and a microfluidic mobility shift readout using the KinaseGlo Luminescent Kinase Assay. The concentrations for ATP were adjusted to the respective Km values of the kinase. D, cellular FGFR autophosphorylation assays; HEK293 cells expressing the indicated FGFR were incubated with NVP-BGJ398 for 40 minutes at the indicated concentrations, and inhibition of FGFR Tyr-phosphorylation was measured by ELISA using a capturing FGFR-specific antibody and the antiphospho-tyrosine antibody PY20 coupled to HRP. In C and D the percentage of phospho-tyrosine inhibition versus dose curves is shown.

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    Figure 2.

    NVP-BGJ398 inhibits proliferation of a subset of cancer cell lines. Scatter plot showing IC50 values expressed in μmol/L of NVP-BGJ398 in cell viability assays of cell lines according to cancer type. A total of 5.9% of the cell lines were sensitive to NVP-BGJ398 at concentrations up to 500 nmol/L. Cell lines with the composite “FGFR genetic alterations” feature are indicated in red. Points were jittered horizontally to improve readability.

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    Figure 3.

    Predictive modeling of NVP-BGJ398 sensitivity using the CCLE features. Top features of drug response identified by categorical-based predictive modeling. Wilcoxon test or Fisher exact test were conducted for continuous or discrete features, respectively. A, fold change or OR as well as P values and Benjamini–Hochberg corrected P values are reported. The number between parentheses for the GeneSets corresponds to the number of genes in the set. B, heatmap for the top 5 features in the model. NVP-BGJ398 response is shown in dark green for the sensitive cell lines and light green for the insensitive cell lines; dark purple is used for discrete features. For GeneSet expression signatures, continuous Z scores are used. P90 and P10 refer to the 90th and 10th percentiles of the GeneSet scores.

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    Figure 4.

    FGFR1 amplification in breast, lung, and osteosarcoma cancer cells is associated with response to NVP-BGJ398. A, box-plot showing FGFR1 copy number expressed as log2 ratio for the 541 cell lines clustered according to cancer type. B, scatter plot of breast, lung, and osteosarcoma cancer cell lines showing the correlation between DNA copy number and transcript expression of FGFR1. Cell lines are colored according to response to NVP-BGJ398. C, effect of NVP-BGJ398 on FGFR downstream signaling as measured by FRS2 Tyr-phosphorylation and Erk1/2 activation. α-Actinin and total Erk1/2 protein levels are shown as a loading control. DMSO, dimethyl sulfoxide. D, stable G292 cell lines expressing short hairpin RNA (shRNA) under the control of a doxycycline (Dox)-inducible promoter were generated via lentiviral infection and puromycin selection. Western blot analysis shows efficient FGFR1 knockdown, p-FRS2 and p-Erk inhibition with shRNA1237 and shRNA1425, as compared with 2 nontargeting shRNAs (NT sh1 and NT sh2). β-Tubulin Western blot analysis is shown as a loading control. E and F, effect of FGFR1-targeting as compared with nontargeting shRNAs on monolayer cell proliferation (E) and anchorage-independent cell growth assays (F) of G292 cells. For monolayer cell proliferation assay, cell growth was monitored at the indicated days after cell seeding, whereas endpoint measurements are given for the soft agar assay (day 15 after cell seeding). G, FGFR1 copy number in a panel of 17 primary human osteosarcoma samples was analyzed by quantitative real-time PCR. Data are shown as average with SEM (n ≥ 2). Br, breast; Ch, chondrosarcoma; CN, copy number; Co, colorectal; En, endometrial; ERK, extracellular signal-regulated kinase; Es, esophagus; Ew, Ewing sarcoma; Ga, gastric; Gl, glioma; HL, hematopoietic and lymphoid tissue; HN, head and neck; Ki, kidney; Li, liver; Lu, lung; Me, melanoma; Ms, mesothelioma; Nb, neuroblastoma; Os, osteosarcoma; Ov, ovarian; Pa, pancreas; Th, thyroid; UT, urinary tract.

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    Figure 5.

    FGFR2 amplification in gastric and colon cancer cell lines is associated with response to NVP-BGJ398. A, box-plot showing FGFR2 copy number expressed as log2 ratio for the 541 cell lines grouped according to cancer type. B, scatter plot of gastric and large intestine cancer cell lines showing the correlation between FGFR2 DNA copy number and transcript expression. C, effect of NVP-BGJ398 on FGFR downstream signaling as measured by FRS2 Tyr-phosphorylation and Erk1/2 activation. α-Actinin and total Erk1/2 protein levels are shown as a loading control. D, SNU16 tumor xenograft–bearing nude rats received NVP-BGJ398 at the indicated doses or vehicle for 14 consecutive days (n = 6 per group). The changes over time in tumor volume are shown. Statistical analysis was conducted by 1-way ANOVA–Dunnett versus vehicle control (*, P < 0.001). E, tumor tissues were recovered 3 and 24 hours after dose treatment and analyzed for FGFR2 Tyr-phosphorylation by Western blot analysis. Total FGFR2 Western blot analysis was conducted to monitor equal loading. Pharmacodynamic analysis of tumors treated with 15 mg/kg NVP-BGJ398 was not feasible due to insufficient material. Br, breast; Ch, chondrosarcoma; Co, colorectal; En, endometrial; Es, esophagus; Ew, Ewing sarcoma; Ga, gastric; Gl, glioma; HL, hematopoietic and lymphoid tissue; HN, head and neck; Ki, kidney; Li, liver; Lu, lung; Me, melanoma; Ms, mesothelioma; Nb, neuroblastoma; Os, osteosarcoma; Ov, ovarian; Pa, pancreas; Th, thyroid; UT, urinary tract.

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    Figure 6.

    FGFR2 amplification in primary human gastric tumors predicts for response to NVP-BGJ398. A, scatter plot of primary human gastric tumors showing the relationship between FGFR2 copy number and transcript expression (n = 49). The gastric tumors CHGA10 and GAM033 with FGFR2 gene amplification [(B) and (C), respectively] were grown subcutaneously in mice. Treatment with NVP-BGJ398 at the indicated doses started when average tumor volume was 150 to 180 mm3 and proceeded for up to 14 or 25 days. Tumor volume changes over the course of treatment are shown. Statistical analysis was conducted by 1-way ANOVA–Dunnett versus vehicle control (*, P < 0.001). D, tumor tissues from primary tumor model GAM033 treated with 15 mg/kg NVP-BGJ398 were recovered 3 hours after the last dose treatment and analyzed for FGFR2 Tyr-phosphorylation and Erk1/2 activation by Western blot analysis. Total FGFR2, Erk1/2, and β-tubulin Western blot analyses were conducted to monitor loading.

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    Figure 7.

    FGF19 amplification in liver cancer cell lines is associated with response to NVP-BGJ398. A, scatter plot showing the correlation between FGF19 copy number and transcript expression of FGF19, FGFR4, and β-Klotho (KLB) in liver cancer cell lines. B, effect of NVP-BGJ398 on FGFR downstream signaling as measured by FRS2 Tyr-phosphorylation and Erk1/2 activation by Western blot analysis after 40 minutes of FGFR inhibitor treatment. Expression of α-actinin indicates equal loading. C, effect of 3 different shRNAs targeting FGFR4 in JHH7 cells upon induction with doxycycline (Dox), compared with a nontargeting shRNA. FGFR4 expression and FRS2 Tyr-phosphorylation are shown in doxycycline-induced and noninduced cell lines. Western blot analysis shows α-actin as a loading control. D, effect of FGFR4 downregulation on monolayer cell proliferation assays at day 7 after cell seeding.

Additional Files

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    Files in this Data Supplement:

    • Supplementary Figures 1-5 - PDF file - 1.4MB, Response to NVP-BGJ398; FGFR pathway modulation by NVP-BGJ398; NVP-BGJ398 - predictive features; FGFR2-c3 mRNA expression in cell lines and FGFR2 DNA copy number in tumors; FGF19 DNA copy number in CCLE cell lines and FGFR3 DNA copy number versus transcript expression in bladder cancer cell lines
    • Supplementary Figure Legends 1-5 - PDF file - 139K
    • Supplementary Tables 1-4 - XML file - 99K, Kinase activity and selectivity for NVP-BGJ398; CCLE cell lines sensitive to NVP-BGJ398; GeneSet expression signatures; FGFR genetic alterations and concomitant mutations
    • Supplementary Table 5 - XML file - 56K, High throughput pharmacological screen of BGJ398 in 517 cancer cell lines
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Cancer Discovery: 2 (12)
December 2012
Volume 2, Issue 12
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FGFR Genetic Alterations Predict for Sensitivity to NVP-BGJ398, a Selective Pan-FGFR Inhibitor
Vito Guagnano, Audrey Kauffmann, Simon Wöhrle, Christelle Stamm, Moriko Ito, Louise Barys, Astrid Pornon, Yao Yao, Fang Li, Yun Zhang, Zhi Chen, Christopher J. Wilson, Vincent Bordas, Mickaël Le Douget, L. Alex Gaither, Jason Borawski, John E. Monahan, Kavitha Venkatesan, Thomas Brümmendorf, David M. Thomas, Carlos Garcia-Echeverria, Francesco Hofmann, William R. Sellers and Diana Graus-Porta
Cancer Discov December 1 2012 (2) (12) 1118-1133; DOI: 10.1158/2159-8290.CD-12-0210

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FGFR Genetic Alterations Predict for Sensitivity to NVP-BGJ398, a Selective Pan-FGFR Inhibitor
Vito Guagnano, Audrey Kauffmann, Simon Wöhrle, Christelle Stamm, Moriko Ito, Louise Barys, Astrid Pornon, Yao Yao, Fang Li, Yun Zhang, Zhi Chen, Christopher J. Wilson, Vincent Bordas, Mickaël Le Douget, L. Alex Gaither, Jason Borawski, John E. Monahan, Kavitha Venkatesan, Thomas Brümmendorf, David M. Thomas, Carlos Garcia-Echeverria, Francesco Hofmann, William R. Sellers and Diana Graus-Porta
Cancer Discov December 1 2012 (2) (12) 1118-1133; DOI: 10.1158/2159-8290.CD-12-0210
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Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

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