Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications

Cancer and Metastasis Reviews

Volumn 34, Issue 3, 2015, Pages 479-496

  Helsten, Teresa ^a   Schwaederle, Maria ^a   Kurzrock, Razelle ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cancer; Cancer therapy; FGF; FGFR; Genetics

Indexed keywords

FIBROBLAST GROWTH FACTOR RECEPTOR; LENVATINIB; PAZOPANIB; PONATINIB; REGORAFENIB; FIBROBLAST GROWTH FACTOR;

ARTICLE; COPY NUMBER VARIATION; GENE AMPLIFICATION; HUMAN; MOLECULAR INTERACTION; NEOPLASM; PRIORITY JOURNAL; PROTEIN TARGETING; SIGNAL TRANSDUCTION; SOMATIC MUTATION; GENETIC DISORDER; GENETICS; METABOLISM; MUTATION; PHYSIOLOGY;

FIBROBLAST GROWTH FACTORS; GENETIC DISEASES, INBORN; HUMANS; MUTATION; NEOPLASMS; RECEPTORS, FIBROBLAST GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84942194341     PISSN: 01677659     EISSN: 15737233     Source Type: Journal    
DOI: 10.1007/s10555-015-9579-8     Document Type: Article

References (192)

1. Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70.
2. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of Cancer: The Next Generation. Cell, 144(5), 646–674. doi:10.1016/j.cell.2011.02.013.
3. Greenman, C., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G., & Stratton, M. R. (2007). Patterns of somatic mutation in human cancer genomes. Nature, 446(7132), 153–158.
4. Torkamani, A., & Schork, N. J. (2008). Prediction of cancer driver mutations in protein kinases. Cancer Research, 68(6), 1675–1682.
5. Muenke, M., Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., & Wilkie, A. O. (1997). A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome. American journal of human genetics, 60(3), 555–564.
6. Robin, N. H., Falk, M. J., & Haldeman-Englert, C. R. (1993). FGFR-Related Craniosynostosis Syndromes. In R. A. Pagon, M. P. Adam, H. H. Ardinger, T. D. Bird, C. R. Dolan, C.-T. Fong, K. Stephens (Eds.), GeneReviews(®). Seattle (WA): University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1455/.
7. Anderson, J., Burns, H. D., Enriquez-Harris, P., Wilkie, A. O., & Heath, J. K. (1998). Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand. Human molecular genetics, 7(9), 1475–1483.
8. He, L., Horton, W., & Hristova, K. (2010). Physical basis behind achondroplasia, the most common form of human dwarfism. The Journal of biological chemistry, 285(39), 30103–30114.
9. Rousseau, F., el Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., & Bonaventure, J. (1996). Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1). Human molecular genetics, 5(4), 509–512.
10. Dodé, C., Teixeira, L., Levilliers, J., Fouveaut, C., Bouchard, P., Kottler, M.-L., & Hardelin, J.-P. (2006). Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS genetics, 2(10), e175.
11. OMIM hypogonatotrophic hypogonadism 2. (n.d.). Retrieved from http://www.omim.org/entry/147950.
12. Dodé, C., Levilliers, J., Dupont, J.-M., De Paepe, A., Le Dû, N., Soussi-Yanicostas, N., & Hardelin, J.-P. (2003). Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nature Genetics, 33(4), 463–465. doi:10.1038/ng1122.
13. Thurman, R. D., Kathir, K. M., Rajalingam, D., & Kumar, T. K. S. (2012). Molecular basis for the Kallmann syndrome-linked fibroblast growth factor receptor mutation. Biochemical and Biophysical Research Communications, 425(3), 673–678. doi:10.1016/j.bbrc.2012.07.104.
14. Trarbach, E. B., Abreu, A. P., Silveira, L. F. G., Garmes, H. M., Baptista, M. T. M., Teles, M. G., & Latronico, A. C. (2010). Nonsense mutations in FGF8 gene causing different degrees of human gonadotropin-releasing deficiency. The Journal of Clinical Endocrinology and Metabolism, 95(7), 3491–3496. doi:10.1210/jc.2010-0176.
15. Turner, N., & Grose, R. (2010). Fibroblast growth factor signalling: from development to cancer. Nature Reviews Cancer, 10(2), 116–129.
16. Dienstmann, R., Rodon, J., Prat, A., Perez-Garcia, J., Adamo, B., Felip, E., & Tabernero, J. (2014). Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO, 25(3), 552–563. doi:10.1093/annonc/mdt419.
17. Baselga, J. (2006). Targeting tyrosine kinases in cancer: the second wave. Science, 312(5777), 1175–1178.
18. Yan, M., Parker, B. A., Schwab, R., & Kurzrock, R. (n.d.). HER2 aberrations in cancer: Implications for therapy. Cancer Treatment Reviews. doi:10.1016/j.ctrv.2014.02.008.
19. Verstovsek, S., Mesa, R. A., Gotlib, J., Levy, R. S., Gupta, V., DiPersio, J. F., & Kantarjian, H. M. (2012). A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New England Journal of Medicine, 366(9), 799–807. doi:10.1056/NEJMoa1110557.
20. Lee, E. B., Fleischmann, R., Hall, S., Wilkinson, B., Bradley, J. D., Gruben, D., & van Vollenhoven, R. F. (2014). Tofacitinib versus Methotrexate in Rheumatoid Arthritis. New England Journal of Medicine, 370(25), 2377–2386. doi:10.1056/NEJMoa1310476.
21. Hubbard, S. R., & Till, J. H. (2000). Protein tyrosine kinase structure and function. Annual review of biochemistry, 69, 373–398.
22. Kim, I., Moon, S.-O., Yu, K.-H., Kim, U.-H., & Koh, G. Y. (2001). A novel fibroblast growth factor receptor-5 preferentially expressed in the pancreas. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1518(1–2), 152–156.
23. Sleeman, M., Fraser, J., McDonald, M., Yuan, S., White, D., Grandison, P., & Murison, J. G. (2001). Identification of a new fibroblast growth factor receptor, FGFR5. Gene, 271(2), 171–182.
24. Klint, P., & Claesson-Welsh, L. (1999). Signal transduction by fibroblast growth factor receptors. Frontiers in bioscience: a journal and virtual library, 4, D165–77.
25. Jin, M., Du, X., & Chen, L. (2012). Cross-talk between FGF and other cytokine signalling pathways during endochondral bone development. Cell biology international, 36(8), 691–696.
26. Horton, W. A. (2006). MOLECULAR PATHOGENESIS OF ACHONDROPLASIA. Growth Genet Horm.
27. Katoh, M. (2008). Cancer genomics and genetics of FGFR2 (Review). International journal of oncology, 33(2), 233–237.
28. Olsen, S. K., Garbi, M., Zampieri, N., Eliseenkova, A. V., Ornitz, D. M., Goldfarb, M., & Mohammadi, M. (2003). Fibroblast Growth Factor (FGF) Homologous Factors Share Structural but Not Functional Homology with FGFs. Journal of Biological \ldots.
29. Itoh, N., & Ornitz, D. M. (2008). Functional evolutionary history of the mouse Fgf gene family. Developmental dynamics: an official publication of the American Association of Anatomists, 237(1), 18–27.
30. Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J. (2012). Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes & development, 26(4), 312–324.
31. Fukumoto, S. (2008). Actions and mode of actions of FGF19 subfamily members. Endocrine journal, 55(1), 23–31.
32. Guillemot, F., & Zimmer, C. (2011). From cradle to grave: the multiple roles of fibroblast growth factors in neural development. Neuron, 71(4), 574–588. doi:10.1016/j.neuron.2011.08.002.
33. Abuharbeid, S., Czubayko, F., & Aigner, A. (2006). The fibroblast growth factor-binding protein FGF-BP. The international journal of biochemistry & cell biology, 38(9), 1463–1468.
34. Zhang, X., Ibrahimi, O. A., Olsen, S. K., Umemori, H., Mohammadi, M., & Ornitz, D. M. (2006). Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. The Journal of biological chemistry, 281(23), 15694–15700.
35. Ornitz, D. M., Xu, J., Colvin, J. S., McEwen, D. G., MacArthur, C. A., Coulier, F., & Goldfarb, M. (1996). Receptor specificity of the fibroblast growth factor family. The Journal of biological chemistry, 271(25), 15292–15297.
36. Itoh, N. (2007). The Fgf families in humans, mice, and zebrafish: their evolutional processes and roles in development, metabolism, and disease. Biological & pharmaceutical bulletin, 30(10), 1819–1825.
37. Hehr, U., & Muenke, M. (1999). Craniosynostosis syndromes: from genes to premature fusion of skull bones. Molecular genetics and metabolism, 68(2), 139–151.
38. Wu, D. Q., Kan, M. K., Sato, G. H., Okamoto, T., & Sato, J. D. (1991). Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors. The Journal of biological chemistry, 266(25), 16778–16785.
39. Böttcher, R. T., Pollet, N., Delius, H., & Niehrs, C. (2004). The transmembrane protein XFLRT3 forms a complex with FGF receptors and promotes FGF signalling. Nature cell biology, 6(1), 38–44.
40. Beenken, A., & Mohammadi, M. (2009). The FGF family: biology, pathophysiology and therapy. Nature reviews Drug discovery, 8(3), 235–253.
41. Hacohen, N., Kramer, S., Sutherland, D., Hiromi, Y., & Krasnow, M. A. (1998). sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell, 92(2), 253–263.
42. Cabrita, M. A., & Christofori, G. (2008). Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis, 11(1), 53–62.
43. Tsang, M., & Dawid, I. B. (2004). Promotion and attenuation of FGF signaling through the Ras-MAPK pathway. Science’s STKE: signal transduction knowledge environment, 2004(228), pe17.
44. Steinberg, F., Zhuang, L., Beyeler, M., Kälin, R. E., Mullis, P. E., Brändli, A. W., & Trueb, B. (2010). The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos. The Journal of biological chemistry, 285(3), 2193–2202.
45. Trueb, B. (2011). Biology of FGFRL1, the fifth fibroblast growth factor receptor. Cellular and molecular life sciences: CMLS, 68(6), 951–964.
46. Rieckmann, T., Zhuang, L., Flück, C. E., & Trueb, B. (2009). Characterization of the first FGFRL1 mutation identified in a craniosynostosis patient. Biochimica et biophysica acta, 1792(2), 112–121.
47. Schild, C., & Trueb, B. (2005). Aberrant expression of FGFRL1, a novel FGF receptor, in ovarian tumors. International journal of molecular medicine, 16(6), 1169–1173.
48. Garcia, S., Dirat, B., Tognacci, T., Rochet, N., Mouska, X., Bonnafous, S., & Gouze, E. (2013). Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice. Science Translational Medicine, 5(203), 203ra–124. doi:10.1126/scitranslmed.3006247.
49. Cohen, M. M. (2003). Neoplasms associated with alterations in fibroblast growth factor receptors. American journal of medical genetics Part A, 119A(2), 97–100.
50. Andreou, A., Lamy, A., Layet, V., Cailliez, D., Gobet, F., Pfister, C., & Frebourg, T. (2006). Early-onset low-grade papillary carcinoma of the bladder associated with Apert syndrome and a germline FGFR2 mutation (Pro253Arg). American journal of medical genetics Part A, 140(20), 2245–2247.
51. Rouzier, C., Soler, C., Hofman, P., Brennetot, C., Bieth, E., & Pedeutour, F. (2008). Ovarian dysgerminoma and Apert syndrome. Pediatric blood & cancer, 50(3), 696–698.
52. Barbosa, M., Almeida, M. do R., Reis-Lima, M., Pinto-Basto, J., & dos Santos, H. G. (2009). Muenke syndrome with osteochondroma. American journal of medical genetics. Part A, 149A(2), 260–261.
53. Bourdeaut, F., Miquel, C., Di Rocco, F., Grison, C., Richer, W., Brugieres, L., & Collet, C. (2013). Germline mutations in FGF receptors and medulloblastomas. American journal of medical genetics Part A, 161A(2), 382–385.
54. Logié, A., Dunois-Lardé, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., & Radvanyi, F. (2005). Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. Human molecular genetics, 14(9), 1153–1160.
55. Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., & Hartmann, A. (2006). Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. Journal of Clinical Investigation, 116(8), 2201–2207.
56. cbioportal. (n.d.). Retrieved from http://www.cbioportal.org/public-portal/index.do.
57. Hattori, Y., Itoh, H., Uchino, S., Hosokawa, K., Ochiai, A., Ino, Y., & Terada, M. (1996). Immunohistochemical detection of K-sam protein in stomach cancer. Clinical cancer research: an official journal of the American Association for Cancer Research, 2(8), 1373–1381.
58. Gust, K. M., McConkey, D. J., Awrey, S., Hegarty, P. K., Qing, J., Bondaruk, J., & Black, P. C. (2013). Fibroblast growth factor receptor 3 is a rational therapeutic target in bladder cancer. Molecular Cancer Therapeutics, 12(7), 1245–1254.
59. Gartside, M. G., Chen, H., Ibrahimi, O. A., Byron, S. A., Curtis, A. V., Wellens, C. L., & Pollock, P. M. (2009). Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma. Molecular cancer research: MCR, 7(1), 41–54.
60. Heist, R. S., Mino-Kenudson, M., Sequist, L. V., Tammireddy, S., Morrissey, L., Christiani, D. C., & Iafrate, A. J. (2012). FGFR1 Amplification in Squamous Cell Carcinoma of The Lung. Journal of Thoracic Oncology, 7(12), 1775–1780.
61. Weiss, J., Sos, M. L., Seidel, D., & Peifer, M. (2010). Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Science translational medicine, 2(62), 62ra93.
62. Albiges, L., Quidville, V., Valent, A., Mathieu, M. C., Drusch, F., Koscielny, S., Andre, F. (2009). FGFR1 amplification and FGF gain in breast cancer. In San Antonio Breast Cancer Symposium. Institut Gustave Roussy, villejuif, France.
63. Jackson, C. C., Medeiros, L. J., & Miranda, R. N. (2010). 8p11 myeloproliferative syndrome: a review. Human Pathology, 41(4), 461–476. doi:10.1016/j.humpath.2009.11.003.
64. Liu, J., Guzman, M. A., Pezanowski, D., Patel, D., Hauptman, J., Keisling, M., & de Chadarévian, J.-P. (2011). FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 24(10), 1327–1335. doi:10.1038/modpathol.2011.98.
65. Grand, E. K., Chase, A. J., Heath, C., Rahemtulla, A., & Cross, N. C. P. (2004). Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074. Leukemia, 18(5), 962–966. doi:10.1038/sj.leu.2403347.
66. Yagasaki, F., Wakao, D., Yokoyama, Y., Uchida, Y., Murohashi, I., Kayano, H., & Bessho, M. (2001). Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation. Cancer Research, 61(23), 8371–8374.
67. Katoh, M., & Katoh, M. (2003). Recombination cluster around FGFR2-WDR11-HTPAPL locus on human chromosome 10q26. International Journal of Molecular Medicine, 11(5), 579–583.
68. Singh, D., Chan, J. M., Zoppoli, P., Niola, F., Sullivan, R., Castano, A., & Iavarone, A. (2012). Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma. Science, 337(6099), 1231–1235.
69. Soria, J.-C., DeBraud, F., Bahleda, R., Adamo, B., Andre, F., Dientsmann, R., & Tabernero, J. (2014). Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO, 25(11), 2244–2251. doi:10.1093/annonc/mdu390.
70. Nakanishi, Y., Akiyama, N., Tsukaguchi, T., Fujii, T., Sakata, K., Sase, H., & Ishii, N. (2014). The Fibroblast Growth Factor Receptor Genetic Status as a Potential Predictor of the Sensitivity to CH5183284/Debio 1347, a Novel Selective FGFR Inhibitor. Molecular Cancer Therapeutics, 13(11), 2547–2558. doi:10.1158/1535-7163.MCT-14-0248.
71. Bellovin, D. I., Palencia, S., Hestir, K., Lee, E., DeYoung, M. P., Brennan, T., & Baker, K. (2014). Abstract 5449: FP-1039/GSK3052230, an FGF ligand trap, enhances VEGF antagonist therapy in preclinical models of RCC and HCC. Cancer Research, 74(19 Supplement), 5449–5449. doi:10.1158/1538-7445.AM2014-5449.
72. Sohl, C. D., Ryan, M. R., Luo, B., Frey, K. M., & Anderson, K. S. (2015). Illuminating the Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance for the FGFR1 Gatekeeper Mutation: The Achilles’ Heel of Targeted Therapy. ACS chemical biology. doi:10.1021/acschembio.5b00014.
73. Chell, V., Balmanno, K., Little, A. S., Wilson, M., Andrews, S., Blockley, L., & Cook, S. J. (2013). Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene, 32(25), 3059–3070. doi:10.1038/onc.2012.319.
74. Byron, S. A., Chen, H., Wortmann, A., Loch, D., Gartside, M. G., Dehkhoda, F., & Pollock, P. M. (2013). The N550K/H mutations in FGFR2 confer differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive inhibitors. Neoplasia (New York, N.Y.), 15(8), 975–988.
75. Crystal, A. S., Shaw, A. T., Sequist, L. V., Friboulet, L., Niederst, M. J., Lockerman, E. L., & Engelman, J. A. (2014). Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science, 346(6216), 1480–1486. doi:10.1126/science.1254721.
76. Harbinski, F., Craig, V. J., Sanghavi, S., Jeffery, D., Liu, L., Sheppard, K. A., & Tiedt, R. (2012). Rescue screens with secreted proteins reveal compensatory potential of receptor tyrosine kinases in driving cancer growth. Cancer Discovery, 2(10), 948–959. doi:10.1158/2159-8290.CD-12-0237.
77. Javidi-Sharifi, N., Traer, E., Martinez, J., Gupta, A., Taguchi, T., Dunlap, J., & Tyner, J. W. (2015). Crosstalk between KIT and FGFR3 Promotes Gastrointestinal Stromal Tumor Cell Growth and Drug Resistance. Cancer Research, 75(5), 880–891. doi:10.1158/0008-5472.CAN-14-0573.
78. Turner, N., Pearson, A., Sharpe, R., Lambros, M., Geyer, F., Lopez-Garcia, M. A., & Ashworth, A. (2010). FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer research, 70(5), 2085–2094. doi:10.1158/0008-5472.CAN-09-3746.
79. Schwaederlé, M., Daniels, G. A., Piccioni, D. E., Fanta, P. T., Schwab, R. B., Shimabukuro, K. A., Kurzrock, R. (2014). Cyclin alterations in diverse cancers: Outcome and co-amplification network. Oncotarget.
80. Wheler, J. J., Parker, B. A., Lee, J. J., Atkins, J. T., Janku, F., Tsimberidou, A. M., Kurzrock, R. (2014). Unique molecular signatures as a hallmark of patients with metastatic breast cancer: Implications for current treatment paradigms. Oncotarget.
81. Schwaederle, M., Parker, B. A., Schwab, R. B., Fanta, P. T., Boles, S. G., Daniels, G. A., & Kurzrock, R. (2014). Molecular tumor board: the University of California-San Diego Moores Cancer Center experience. The Oncologist, 19(6), 631–636. doi:10.1634/theoncologist.2013-0405.
82. Tsimberidou, A.-M., Iskander, N. G., Hong, D. S., Wheler, J. J., Falchook, G. S., Fu, S., & Kurzrock, R. (2012). Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clinical cancer research: an official journal of the American Association for Cancer Research, 18(22), 6373–6383. doi:10.1158/1078-0432.CCR-12-1627.
83. omim.org. (n.d.). Retrieved from http://www.omim.org/.
84. Cohen, M. M. (1993). Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. American journal of medical genetics, 45(3), 300–307.
85. Vogels, A., & Fryns, J.-P. (2006). Pfeiffer syndrome. Orphanet journal of rare diseases, 1, 19.
86. Ibrahimi, O. A., Zhang, F., Eliseenkova, A. V., Linhardt, R. J., & Mohammadi, M. (2004). Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity. Human Molecular Genetics, 13(1), 69–78. doi:10.1093/hmg/ddh011.
87. Davies, H., Hunter, C., Smith, R., Stephens, P., Greenman, C., Bignell, G., Futreal, P. A. (2005). Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer.
88. Ruhe, J. E., Streit, S., Hart, S., Wong, C.-H., Specht, K., Knyazev, P., Ullrich, A. (2007). Genetic Alterations in the Tyrosine Kinase Transcriptome of Human Cancer Cell Lines. Cancer Research.
89. White, K. E., Cabral, J. M., Davis, S. I., Fishburn, T., Evans, W. E., Ichikawa, S., & Econs, M. J. (2005). Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. American journal of human genetics, 76(2), 361–367.
90. Riminucci, M., Collins, M. T., Fedarko, N. S., Cherman, N., Corsi, A., White, K. E., & Gehron Robey, P. (2003). FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. Journal of Clinical Investigation, 112(5), 683–692.
91. Moloney, D. M., Slaney, S. F., Oldridge, M., Wall, S. A., Sahlin, P., Stenman, G., & Wilkie, A. O. (1996). Exclusive paternal origin of new mutations in Apert syndrome. Nature genetics, 13(1), 48–53.
92. Miraoui, H., Ringe, J., & Häupl, T. (2010). Increased EFG-and PDGFα-receptor signaling by mutant FGF-receptor 2 contributes to osteoblast dysfunction in Apert craniosynostosis. Human molecular \ldots.
93. Pollock, P. M., Gartside, M. G., Dejeza, L. C., Powell, M. A., Mallon, M. A., Davies, H., & Goodfellow, P. J. (2007). Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. Oncogene, 26(50), 7158–7162.
94. Byron, S. A., Gartside, M., Powell, M. A., Wellens, C. L., Gao, F., Mutch, D. G., & Pollock, P. M. (2012). FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features. PLoS ONE, 7(2), e30801.
95. Passos-Bueno, M. R., Wilcox, W. R., Jabs, E. W., Serti, A. L., Alonso, L. G., & Kitoh, H. (1999). Clinical spectrum of fibroblast growth factor receptor mutations. Human Mutation, 14(2), 115–125.
96. Reardon, W., Winter, R. M., Rutland, P., Pulleyn, L. J., Jones, B. M., & Malcolm, S. (1994). Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nature genetics, 8(1), 98–103.
97. Glaser, R. L., Jiang, W., Boyadjiev, S. A., Tran, A. K., Zachary, A. A., Van Maldergem, L., & Jabs, E. W. (2000). Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. American journal of human genetics, 66(3), 768–777.
98. Jang, J. H., Shin, K. H., & Park, J. G. (2001). Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. Cancer Research, 61(9), 3541–3543.
99. Chokdeemboon, C., Mahatumarat, C., Rojvachiranonda, N., Tongkobpetch, S., Suphapeetiporn, K., & Shotelersuk, V. (2013). FGFR1 and FGFR2 mutations in Pfeiffer syndrome. The Journal of craniofacial surgery, 24(1), 150–152.
100. Cornejo-Roldan, L. R., Roessler, E., & Muenke, M. (1999). Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome - Springer. Human genetics.
101. Chen, L., Adar, R., Yang, X., Monsonego, E. O., Li, C., Hauschka, P. V., & Deng, C. X. (1999). Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. Journal of Clinical Investigation, 104(11), 1517–1525.
102. Monsonego-Ornan, E., Adar, R., Feferman, T., Segev, O., & Yayon, A. (2000). The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation. Molecular and cellular biology, 20(2), 516–522.
103. Henderson, J. E., Naski, M. C., Aarts, M. M., Wang, D., Cheng, L., Goltzman, D., & Ornitz, D. M. (2000). Expression of FGFR3 with the G380R Achondroplasia Mutation Inhibits Proliferation and Maturation of CFK2 Chondrocytic Cells. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research, 15(1), 155–165.
104. Knowles, M. A. (2008). Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Future oncology (London, England), 4(1), 71–83.
105. Ahmad, I., Iwata, T., & Leung, H. Y. (2012). Mechanisms of FGFR-mediated carcinogenesis. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1823(4), 850–860.
106. Delezoide, A. L., Lasselin-Benoist, C., Legeai-Mallet, L., Brice, P., Senée, V., Yayon, A., & Bonaventure, J. (1997). Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses. Human molecular genetics, 6(11), 1899–1906.
107. Wilcox, W. R., Tavormina, P. L., Krakow, D., Kitoh, H., Lachman, R. S., Wasmuth, J. J., & Rimoin, D. L. (1998). Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia. American journal of medical genetics, 78(3), 274–281.
108. Brodie, S. G., Kitoh, H., Lachman, R. S., Nolasco, L. M., Mekikian, P. B., & Wilcox, W. R. (1999). Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations. American journal of medical genetics, 84(5), 476–480.
109. Di Martino, E., Tomlinson, D. C., & Knowles, M. A. (2012). A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges. Advances in Urology, 2012, e429213. doi:10.1155/2012/429213.
110. Salgia, R. (2014). Fibroblast growth factor signaling and inhibition in non-small cell lung cancer and their role in squamous cell tumors. Cancer Medicine, 3(3), 681–692. doi:10.1002/cam4.238.
111. Liao, R. G., Jung, J., Tchaicha, J., Wilkerson, M. D., Sivachenko, A., Beauchamp, E. M., & Hammerman, P. S. (2013). Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma. Cancer Research, 73(16), 5195–5205. doi:10.1158/0008-5472.CAN-12-3950.
112. Webster, M. K., D’Avis, P. Y., Robertson, S. C., & Donoghue, D. J. (1996). Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II. Molecular and cellular biology, 16(8), 4081–4087.
113. Lievens, P. M.-J., & Liboi, E. (2003). The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. The Journal of biological chemistry, 278(19), 17344–17349.
114. Otsuka, M., Mizuki, M., Fujita, J., Kang, S., & Kanakura, Y. (2011, January). Constitutively active FGFR3 with Lys650Glu mutation enhances bortezomib sensitivity in plasma cell malignancy. Anticancer Research.
115. Walker, B. A., Murdoch, J. L., McKusick, V. A., Langer, L. O., & Beals, R. K. (1971). Hypochondroplasia. American journal of diseases of children (1960), 122(2), 95–104.
116. Bellus, G. A., McIntosh, I., Smith, E. A., Aylsworth, A. S., Kaitila, I., Horton, W. A., & Francomano, C. A. (1995). A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nature genetics, 10(3), 357–359.
117. Bellus, G. A., Garber, A. T., Bryke, C. R., Weaver, C. A., Speiser, P. W., Webster, M. K., & Spector, E. B. (2000). FGFR3 Mutations K650N and K650Q Cause Hypochondroplasia. Genetics in Medicine, 2(1), 76–76.
118. Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., & Bonaventure, J. (2006). Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia. European Journal of Human Genetics, 14(12), 1240–1247.
119. Abdel-Salam, G. M. H., Flores-Sarnat, L., El-Ruby, M. O., Parboosingh, J., Bridge, P., Eid, M. M., & Temtamy, S. A. (2011). Muenke syndrome with pigmentary disorder and probable hemimegalencephaly: An expansion of the phenotype. American journal of medical genetics Part A, 155A(1), 207–214.
120. Cancer Genome Atlas Network. (2012). Comprehensive molecular portraits of human breast tumours. Nature, 490(7418), 61–70. doi:10.1038/nature11412.
121. Shiang, C. Y., Qi, Y., Wang, B., Lazar, V., Wang, J., Fraser Symmans, W., & Pusztai, L. (2010). Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate. Breast Cancer Research and Treatment, 123(3), 747–755.
122. Brunello, E., Brunelli, M., Bogina, G., Caliò, A., Manfrin, E., Nottegar, A., & Bonetti, F. (2012). FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma. Journal of experimental & clinical cancer research: CR, 31, 103.
123. Elbauomy Elsheikh, S., Green, A. R., Lambros, M. B. K., Turner, N. C., Grainge, M. J., Powe, D., & Reis-Filho, J. S. (2007). FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Research, 9(2), R23.
124. The Cancer Genome Atlas Research Network. (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507(7492), 315–322. doi:10.1038/nature12965.
125. Freier, K., Schwaenen, C., Sticht, C., Flechtenmacher, C., Mühling, J., Hofele, C., & Joos, S. (2007). Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral oncology, 43(1), 60–66.
126. Goke, F., Franzen, A., Roopika, M., Schroeck, A., Kirsten, R., Boehm, D., & Perner, S. (2013). In 25th European Congress of Pathology. Portugal: Lisbon.
127. The Cancer Genome Atlas Research Network. (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 513(7517), 202–209. doi:10.1038/nature13480.
128. Xie, L., Su, X., Zhang, L., Yin, X., Tang, L., Zhang, X., Ji, Q. (2013). FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547. Clinical cancer research: an official journal of the American Association for Cancer Research.
129. Matsumoto, K., Arao, T., Hamaguchi, T., Shimada, Y., Kato, K., Oda, I., & Yamada, Y. (2012). FGFR2 gene amplification and clinicopathological features in gastric cancer. British Journal of Cancer, 106(4), 727–732.
130. Cancer Genome Atlas Research Network. (2011). Integrated genomic analyses of ovarian carcinoma. Nature, 474(7353), 609–615.
131. Barretina, J., Taylor, B. S., Banerji, S., Ramos, A. H., Lagos-Quintana, M., Decarolis, P. L., & Singer, S. (2010). Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nature genetics, 42(8), 715–721.
132. Hodis, E., Watson, I. R., Kryukov, G. V., Arold, S. T., Imielinski, M., Theurillat, J.-P., & Chin, L. (2012). A Landscape of Driver Mutations in Melanoma. Cell, 150(2), 251–263. doi:10.1016/j.cell.2012.06.024.
133. Cancer Genome Atlas Research Network, Kandoth, C., Schultz, N., Cherniack, A. D., Akbani, R., Liu, Y., & Levine, D. A. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497(7447), 67–73.
134. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. (2002)., Published online: 03 December 2002; | doi:10.1038/sj.ejhg.5200883, 10(12). doi:10.1038/sj.ejhg.5200883.
135. Williams, S. V., Hurst, C. D., & Knowles, M. A. (2013). Oncogenic FGFR3 gene fusions in bladder cancer. Human molecular genetics, 22(4), 795–803.
136. Rosty, C., Aubriot, M.-H., Cappellen, D., Bourdin, J., Cartier, I., Thiery, J. P., & Radvanyi, F. (2005). Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation. Molecular Cancer, 4, 15. doi:10.1186/1476-4598-4-15.
137. Taylor, J. G., Cheuk, A. T., Tsang, P. S., Chung, J.-Y., Song, Y. K., Desai, K., & Khan, J. (2009). Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. The Journal of Clinical Investigation, 119(11), 3395–3407. doi:10.1172/JCI39703.
138. Turkington, R. C., Longley, D. B., Allen, W. L., Stevenson, L., McLaughlin, K., Dunne, P. D., & Johnston, P. G. (2014). Fibroblast growth factor receptor 4 (FGFR4): a targetable regulator of drug resistance in colorectal cancer. Cell Death & Disease, 5(2), e1046. doi:10.1038/cddis.2014.10.
139. Persson, F., Winnes, M., Andrén, Y., Wedell, B., Dahlenfors, R., Asp, J., & Stenman, G. (2008). High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes. Oncogene, 27(21), 3072–3080. doi:10.1038/sj.onc.1210961.
140. Arai, Y., Totoki, Y., Hosoda, F., Shirota, T., Hama, N., Nakamura, H., & Shibata, T. (2014). Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology, 59(4), 1427–1434. doi:10.1002/hep.26890.
141. Wu, Y.-M., Su, F., Kalyana-Sundaram, S., Khazanov, N., Ateeq, B., Cao, X., Chinnaiyan, A. M. (2013). Identification of Targetable FGFR Gene Fusions in Diverse Cancers. Cancer discovery.
142. Cancer Genome Atlas Research Network. (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489(7417), 519–525. doi:10.1038/nature11404.
143. Shah, S. P., Roth, A., Goya, R., Oloumi, A., Ha, G., Zhao, Y., & Aparicio, S. (2012). The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature, 486(7403), 395–399.
144. Banerji, S., Cibulskis, K., Rangel-Escareno, C., Brown, K. K., Carter, S. L., Frederick, A. M., & Meyerson, M. (2012). Sequence analysis of mutations and translocations across breast cancer subtypes. Nature, 486(7403), 405–409.
145. Stephens, P. J., Tarpey, P. S., Davies, H., Van Loo, P., Greenman, C., Wedge, D. C., & Stratton, M. R. (2012). The landscape of cancer genes and mutational processes in breast cancer. Nature, 486(7403), 400–404.
146. Gaykalova, D. A., Mambo, E., Choudhary, A., Houghton, J., Buddavarapu, K., Sanford, T., & Sun, W. (2014). Novel insight into mutational landscape of head and neck squamous cell carcinoma. PloS One, 9(3), e93102. doi:10.1371/journal.pone.0093102.
147. Mountzios, G., Rampias, T., & Psyrri, A. (2014). The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. doi:10.1093/annonc/mdu143.
148. The Cancer Genome Atlas Research Network. (2014). Comprehensive molecular profiling of lung adenocarcinoma. Nature, 511(7511), 543–550. doi:10.1038/nature13385.
149. Imielinski, M., Berger, A. H., Hammerman, P. S., Hernandez, B., Pugh, T. J., Hodis, E., & Meyerson, M. (2012). Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell, 150(6), 1107–1120.
150. Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., & Wilson, R. K. (2008). Somatic mutations affect key pathways in lung adenocarcinoma. Nature, 455(7216), 1069–1075.
151. Taylor, B. S., Schultz, N., Hieronymus, H., Gopalan, A., Xiao, Y., Carver, B. S., & Gerald, W. L. (2010). Integrative genomic profiling of human prostate cancer. Cancer Cell, 18(1), 11–22.
152. The Cancer Genome Atlas Research Network. (2013). Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499(7456), 43–49. doi:10.1038/nature12222.
153. ancer Genome Atlas Network. (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487(7407), 330–337. doi:10.1038/nature11252.
154. McLendon, R., Friedman, A., Bigner, D., Van Meir, E. G., Brat, D. J., Mastrogianakis, M. G., & Thomson, E. (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 455(7216), 1061–1068.
155. Ho, A. S., Kannan, K., Roy, D. M., Morris, L. G. T., Ganly, I., Katabi, N., & Chan, T. A. (2013). The mutational landscape of adenoid cystic carcinoma. Nature genetics, 45(7), 791–798.
156. Brat, D. J. (2014). Integrative Genomic Characterization of Lower Grade Gliomas. Neuro-Oncology, 16, iii3. doi:10.1093/neuonc/nou206.11.
157. Cancer Genome Atlas Research Network. (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. The New England journal of medicine, 368(22), 2059–2074.
158. Seshagiri, S., Stawiski, E. W., Durinck, S., Modrusan, Z., Storm, E. E., Conboy, C. B., & de Sauvage, F. J. (2012). Recurrent R-spondin fusions in colon cancer. Nature, 488(7413), 660–664.
159. clinicaltrials.gov. (n.d.). Retrieved from http://clinicaltrials.gov/ct2/home.
160. Smyth, E. C., Turner, N. C., Popat, S., Morgan, S., Owen, K., Gillbanks, A., & Cunningham, D. (2013). FGFR: Proof-of-concept study of AZD4547 in patients with FGFR1 or FGFR2 amplified tumours. ASCO Meeting Abstracts, 31(15_suppl), TPS2626.
161. Zhang, J., Zhang, L., Su, X., Li, M., Xie, L., Malchers, F., & Gavine, P. R. (2012). Translating the therapeutic potential of AZD4547 in FGFR1-amplified non-small cell lung cancer through the use of patient-derived tumor xenograft models. Clinical cancer research: an official journal of the American Association for Cancer Research, 18(24), 6658–6667.
162. Johnson, P. J., Qin, S., Park, J.-W., Poon, R. T. P., Raoul, J.-L., Philip, P. A., & Cheng, A.-L. (2013). Brivanib Versus Sorafenib As First-Line Therapy in Patients With Unresectable, Advanced Hepatocellular Carcinoma: Results From the Randomized Phase III BRISK-FL Study. Journal of Clinical Oncology, JCO, 2012(48), 4410. doi:10.1200/JCO.2012.48.4410.
163. Huynh, H., Ngo, V. C., Fargnoli, J., Ayers, M., Soo, K. C., Koong, H. N., & Tran, E. (2008). Brivanib Alaninate, a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Tyrosine Kinases, Induces Growth Inhibition in Mouse Models of Human Hepatocellular Carcinoma. Clinical Cancer Research, 14(19), 6146–6153.
164. Siu, L. L., Shapiro, J. D., Jonker, D. J., Karapetis, C. S., Zalcberg, J. R., Simes, J., NCIC Clinical Trials Group and AGITG. (2012). Phase III randomized trial of cetuximab (CET) plus either brivanib alaninate (BRIV) or placebo in patients (pts) with metastatic (MET) chemotherapy refractory K-RAS wild-type (WT) colorectal carcinoma (CRC): The NCIC Clinical Trials Group and AGITG CO.20 trial. ASCO Meeting Abstracts, 30(4_suppl), 386.
165. Meulenbeld, H. J., Bleuse, J. P., Vinci, E. M., Raymond, E., Vitali, G., Santoro, A., & de Wit, R. (2013). Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU international, 111(1), 44–52. doi:10.1111/j.1464-410X.2012.11404.x.
166. Cohen, R. B., Jones, S. F., Aggarwal, C., von Mehren, M., Cheng, J., Spigel, D. R., & Burris, H. A. (2009). A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15(21), 6694–6701. doi:10.1158/1078-0432.CCR-09-1445.
167. Motzer, R. J., Porta, C., Vogelzang, N. J., Sternberg, C. N., Szczylik, C., Zolnierek, J., & Escudier, B. (2014). Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. The Lancet. Oncology, 15(3), 286–296. doi:10.1016/S1470-2045(14)70030-0.
168. Motzer, R. J., Porta, C., Bjarnason, G. A., Szcylik, C., Rha, S. Y., Esteban, E., Escudier, B. J. (2012). Phase III trial of dovitinib (TKI258) versus sorafenib in patients with metastatic renal cell carcinoma after failure of anti-angiogenic (VEGF-targeted and mTOR inhibitor) therapies. ASCO Meeting Abstracts, 30(15_suppl), TPS4683.
169. Angevin, E., Lin, C., Pande, A. U., & Lopez, J. A. (2010). A phase I/II study of dovitinib (TKI258), a FGFR and VEGFR inhibitor, in patients (pts) with advanced or metastatic renal cell cancer: phase I results. ASCO Meeting \ldots.
170. Dienstmann, R., Bahleda, R., Adamo, B., Rodon, J., Varga, A., Gazzah, A., & Soria, J.-C. (2014). Abstract CT325: First in human study of JNJ-42756493, a potent pan fibroblast growth factor receptor (FGFR) inhibitor in patients with advanced solid tumors. Cancer Research, 74(19 Supplement), CT325–CT325. doi:10.1158/1538-7445.AM2014-CT325.
171. Schlumberger, M., Tahara, M., Wirth, L. J., Robinson, B., Brose, M. S., Elisei, R., Sherman, S. I. (2014). A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT) [abstract]. In Journal of clinical oncology: official journal of the American Society of Clinical Oncology (p. LBA6008).
172. Tohyama, O., Matsui, J., Kodama, K., Hata-Sugi, N., Kimura, T., Okamoto, K., & Funahashi, Y. (2014). Antitumor Activity of Lenvatinib (E7080): An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models. Journal of Thyroid Research, 2014, e638747. doi:10.1155/2014/638747.
173. Andre, F., Daly, F., Azim, H. A., Agrapart, V., Goulioti, T., Pinto, A. C. D. C. P., Cortes, J. (2014). FINESSE: An open, three-cohort, phase II trial testing oral administration of lucitanib in patients with FGFR1-amplified or nonamplified estrogen receptor-positive metastatic breast cancer. Journal of Clinical Oncology, 32:5s(suppl; abstr TPS1134). Retrieved from http://meetinglibrary.asco.org/content/126911-144.
174. Bello, E., Taraboletti, G., Colella, G., Zucchetti, M., Forestieri, D., Licandro, S. A., & Damia, G. (2013). The Tyrosine Kinase Inhibitor E-3810 Combined with Paclitaxel Inhibits the Growth of Advanced-Stage Triple-Negative Breast Cancer Xenografts. Molecular Cancer Therapeutics, 12(2), 131–140.
175. Bello, E., Colella, G., Scarlato, V., Oliva, P., Berndt, A., Valbusa, G., & Camboni, G. (2011). E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Research, 71(4), 1396–1405.
176. Carter, E. P., Fearon, A. E., & Grose, R. P. (n.d.). Careless talk costs lives: fibroblast growth factor receptor signalling and the consequences of pathway malfunction. Trends in Cell Biology. doi:10.1016/j.tcb.2014.11.003.
177. Pan, B.-S., Chan, G. K. Y., Chenard, M., Chi, A., Davis, L. J., Deshmukh, S. V., & Dinsmore, C. J. (2010). MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Research, 70(4), 1524–1533.
178. Hanna, N. H., Kaiser, R., Sullivan, R. N., Aren, O. R., Ahn, M.-J., Tiangco, B., Kim, J. H. (2013). Lume-lung 2: A multicenter, randomized, double-blind, phase III study of nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy. ASCO Meeting Abstracts, 31(15_suppl), 8034.
179. Richeldi, L., du Bois, R. M., Raghu, G., Azuma, A., Brown, K. K., Costabel, U., & Collard, H. R. (2014). Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. New England Journal of Medicine, 370(22), 2071–2082. doi:10.1056/NEJMoa1402584.
180. Kristensen, G., Harter, P., Trédan, O., Sailer, M. O., Bamias, A., Colombo, N., Bois, A. D. (2014). Independent review of AGO-OVAR 12, a GCIG/ENGOT-Intergroup phase III trial of nintedanib (N) in first-line therapy for ovarian cancer (OC). Journal of Clinical Oncology, 32:5s(suppl; abstr 5556^). Retrieved from http://meetinglibrary.asco.org/content/130341-144.
181. Guagnano, V., Furet, P., Spanka, C., Bordas, V., Le Douget, M., Stamm, C., & Graus Porta, D. (2011). Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. Journal of Medicinal Chemistry, 54(20), 7066–7083. doi:10.1021/jm2006222.
182. Guagnano, V., Kauffmann, A., Wöhrle, S., Stamm, C., Ito, M., Barys, L., & Graus-Porta, D. (2012). FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discovery, 2(12), 1118–1133. doi:10.1158/2159-8290.CD-12-0210.
183. Konecny, G. E., Kolarova, T., O’Brien, N. A., Winterhoff, B., Yang, G., Qi, J., Slamon, D. J. (2013). Activity of the Fibroblast Growth Factor Receptor Inhibitors Dovitinib (TKI258) and NVP-BGJ398 in Human Endometrial Cancer Cells. Molecular Cancer Therapeutics.
184. Motzer, R. J., Hutson, T. E., McCann, L., Deen, K., & Choueiri, T. K. (2014). Overall survival in renal-cell carcinoma with pazopanib versus sunitinib. The New England Journal of Medicine, 370(18), 1769–1770. doi:10.1056/NEJMc1400731.
185. Kasper, B., Sleijfer, S., Litière, S., Marreaud, S., Verweij, J., Hodge, R. A., & van der Graaf, W. T. A. (2014). Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO, 25(3), 719–724. doi:10.1093/annonc/mdt586.
186. O’Hare, T., Shakespeare, W. C., Zhu, X., Eide, C. A., Rivera, V. M., Wang, F., & Clackson, T. (2009). AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell, 16(5), 401–412.
187. Cortes, J. E., Kim, D.-W., Pinilla-Ibarz, J., le Coutre, P., Paquette, R., Chuah, C., & Investigators, P. A. C. E. (2013). A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. The New England Journal of Medicine, 369(19), 1783–1796. doi:10.1056/NEJMoa1306494.
188. Demetri, G. D., Reichardt, P., Kang, Y.-K., Blay, J.-Y., Rutkowski, P., Gelderblom, H., & GRID study investigators. (2013). Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet, 381(9863), 295–302. doi:10.1016/S0140-6736(12)61857-1.
189. Grothey, A., Van Cutsem, E., Sobrero, A., Siena, S., Falcone, A., Ychou, M., & CORRECT Study Group. (2013). Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet, 381(9863), 303–312. doi:10.1016/S0140-6736(12)61900-X.
190. Ochiiwa, H., Fujita, H., Itoh, K., Sootome, H., Hashimoto, A., Fujioka, Y., & Utsugi, T. (2013). Abstract A270: TAS-120, a highly potent and selective irreversible FGFR inhibitor, is effective in tumors harboring various FGFR gene abnormalities. Molecular Cancer Therapeutics, 12(11 Supplement), A270–A270. doi:10.1158/1535-7163.TARG-13-A270.
191. Powers, C. J., McLeskey, S. W., & Wellstein, A. (2000). Fibroblast growth factors, their receptors and signaling. Endocrine-Related Cancer, 7(3), 165–197.
192. Itoh, N., & Ornitz, D. M. (2004). Evolution of the Fgf and Fgfr gene families. Trends in Genetics, 20(11), 563–569. doi:10.1016/j.tig.2004.08.007.