FGF Receptor inhibitors: Role in cancer therapy

Current Oncology Reports

Volumn 14, Issue 2, 2012, Pages 111-119

  Daniele, Gennaro ^a   Corral, Jesus ^a   Molife, L Rhoda ^a   De Bono, Johann S ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

Angiogenesis; Angiokinase inhibitors; AZD4547; BIBF 1120; Breast cancer; Brivanib; Dovotinib; FGF; FGFR; Fibroblast growth factor signaling; Multitargeted receptor tyrosine kinase

Indexed keywords

AZD 4547; BGJ 398; BRIVANIB; BRIVANIB ALANINATE; DOVITINIB; DUAL SPECIFICITY PHOSPHATASE 6; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR RECEPTOR; FIBROBLAST GROWTH FACTOR RECEPTOR 5; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IMC A1; LENVATINIB; MASITINIB; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE PHOSPHATASE 1; MONOCLONAL ANTIBODY IMC A1; MONOCLONAL ANTIBODY PRO 001; MONOCLONAL ANTIBODY R3; NINTEDANIB; ORANTINIB; OXALIPLATIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOLIPASE C GAMMA; PLACEBO; PRO 001; PROTEIN KINASE B; PROTEIN TYROSINE KINASE INHIBITOR; R3MAB; RAF PROTEIN; RAS PROTEIN; SORAFENIB; SPROUTY PROTEIN; STAT PROTEIN; TK 1258; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANGIOGENESIS; ARTICLE; ASTROCYTOMA; BLADDER CANCER; BONE MARROW SUPPRESSION; BRAIN CANCER; BREAST CANCER; BREAST METASTASIS; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; COLORECTAL CANCER; DIARRHEA; DRUG TARGETING; ENDOMETRIUM CANCER; ESOPHAGUS CANCER; FATIGUE; FGFR1 GENE; FGFR2 GENE; FGFR3 GENE; FGFR4 GENE; GASTROINTESTINAL DISEASE; GENE AMPLIFICATION; GENE MUTATION; GENETIC ASSOCIATION; GLIOBLASTOMA; HUMAN; HYPERTENSION; HYPERTRANSAMINASEMIA; KIDNEY CANCER; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MOUTH CANCER; MULTIPLE MYELOMA; NAUSEA; OVARY CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PLEURA EFFUSION; PLEURAL PAIN; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PROSTATE CANCER; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECEPTOR UPREGULATION; RHABDOMYOSARCOMA; SARCOMA; SEMINOMA; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN DISEASE; SOFT TISSUE SARCOMA; STOMACH CANCER; THROMBOSIS; THYROID CANCER; UTERINE CERVIX CANCER; VASCULAR DISEASE; VOMITING; DRUG ANTAGONISM; METABOLISM; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

CELL SURVIVAL; FIBROBLAST GROWTH FACTORS; HUMANS; NEOPLASMS; RECEPTORS, FIBROBLAST GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84860878985     PISSN: 15233790     EISSN: 15346269     Source Type: Journal    
DOI: 10.1007/s11912-012-0225-0     Document Type: Article

References (93)

1. Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8: 235-53.
2. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Canc. 2010;10: 116-29. Excellent review of FGF signalling and role in cancer.
3. Johnson DE, Williams LT. Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res. 1993;60: 1-41.
4. Naski MC, Ornittz DM. FGF signalling in skeletal development. Front Biosci. 1998;3: 781-94.
5. Chellaiah AT, McEwen DG, Werner S, et al. Fibroblast growth factor receptor (FGFR) 3. Alternative splicing in immunoglobulinlike domain III creates a receptor highly specific for acidic FGF/ FGF-1. J Biol Chem. 1994;269: 11620-7. (Pubitemid 24200387)
6. Eswarakumar VP, Lax I, Schlessinger J. Cellular signalling of fibroblast growth factor receptors. Cytokine Growth Factor Rec. 2005;16: 139-49. (Pubitemid 40616112)
7. Altomare DA, Testa JR. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005;24: 7455-64. (Pubitemid 41637985)
8. Hart KC, Robertson SC, Kanemitsu NY, et al. Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4. Oncogene. 2000;19: 3309-20. (Pubitemid 30487417)
9. Kang S, Elf S, Dong T, et al. Fibroblast growth factor receptor 3 associates with and tyrosine phosphorylates p90 RSK2, leading to RSK2 activation that mediates hematopoietic transformation. Mol Cell Biol. 2009;29: 2105-17.
10. Thien CB, Langodn WY. Cbl: many adaptations to regulate protein tyrosine kinases. Nature Rev Mol Cell Biol. 2001;2: 294-307.
11. Presta M, Dell'Era P, Mitola S, et al. Fibroblast growth factor/ fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16: 159-78. (Pubitemid 40616114)
12. Kandel J, Bossy-Wetzel E, Radvanyi F, et al. Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell. 1991;66: 1095-104. (Pubitemid 121001400)
13. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003;83: 835-70. (Pubitemid 36828927)
14. Risau W. Angiogenic growth factors. Prog Growth Factor Res. 1990;2: 71-9. (Pubitemid 120040341)
15. Fujii T, Kuwano H. Regulation of the expression balance of angiopoietin-1 and angiopoietin-2 by Shh and FGF-2. In Vitro Cell Dev Biol Anim. 2010;46: 487-91.
16. Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun. 1992;189: 824-31. (Pubitemid 23032448)
17. Compagni A, Wilgenbus P, Impagnatiello M-A, et al. Fibroblast growth factors are required for efficient tumor angiogenesis. Cancer Res. 2000;60: 7163-9. (Pubitemid 32059199)
18. Giavazzi R, Sennino B, Coltrini D, et al. Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. Am J Pathol. 2003;162: 1913-26. (Pubitemid 36613049)
19. Nissen LJ, Cao R, Hedlund E-M, et al. Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularisation and metastasis. J Clin Invest. 2007;117: 2766-77. (Pubitemid 47529608)
20. Lieu C, Heymach J, Overman M, et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res. 2011;17: 1-10. The role of targeting FGF signalling in antiangiogenic therapy.
21. Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signalling in latestage pancreatic islet tumors. Cancer Cell. 2005;8: 299-309. (Pubitemid 41443415)
22. Allen E, Walters I, Hanahan D. Brivanib, a dual FGF/VEGF inhibitor, is active both as first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin Cancer Res. 2001;17: 5299-310.
23. Pietras K, Pahler J, Bergers G, Hanahan D. Functions of paracrine PDGF signalling in the proangiogenic stroma revealed by pharmacological targeting. PLos Med. 2008;5: 19.
24. Kopetz S, Hoff PM, Morris JS, et al. Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol. 2009;24: 8252.
25. Batchelor TT, Sorenson AG, di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11: 83-95. (Pubitemid 46075199)
26. Birrer MJ, Johnson ME, Hao K, et al. Whole genome oligonucleotide-based array comparative genomic hybridization analysus identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J Clin Oncol. 2007;25: 2281-7. (Pubitemid 46954656)
27. Dorkin TJ, Robinson MC, Marsh C, et al. FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease. Oncogene. 1999;18: 2755-61. (Pubitemid 29237664)
28. Giri D, Ropiquet F, Ittmann M. Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer. Clin Cancer Res. 1999;5: 1063-71. (Pubitemid 29233220)
29. Ropiquet F, Giri D, Kwabi-Addo B, et al. Increased expression of fibroblast growth factor in human prostatic intraepithelial neoplasia and prostate cancer. Cancer Res. 2000;60: 4245-50. (Pubitemid 30636612)
30. Kwabi-Addo B, Ozen M, Ittmann M. The role of fibroblast growth factors and their receptors in prostate cancer. Endo-rel Cancer. 2004;11: 709-24. (Pubitemid 40065546)
31. Dorkin TJ, Robinson MC, Marsh C, et al. ?FGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8. J Path. 1999;189: 564-9.
32. Mattila MM, Harkonen PL. Role of fibroblast growth factor 8 in growth and progression of hormonal cancer. Cytokine Growth Factor Rev. 2007;18: 257-66. (Pubitemid 46891289)
33. Shimokawa T, Furukawa Y, Sakai M, et al. Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the [beta}-catenin/T-cell factor complex. Cancer Res. 2003;63: 6116-20. (Pubitemid 37255147)
34. Courjal F, Cuny M, Simony-Lafontaine J, et al. Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 1997;57: 4360-7. (Pubitemid 27413447)
35. Turner N, Pearson A, Sharpe R, et al. FGFR1 expression drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res. 2010;70: 2085-94.
36. Freier K, Schwaenen C, Sticht C, et al. Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol. 2007;43: 60-6. (Pubitemid 46162249)
37. Ishizuka T, Tanabe C, Sakamoto H, et al. Gene amplification profiling of esophageal squamous cell carcinoimas by DNA array CGH. Biochem Biophys Res Commun. 2002;296: 152-5. (Pubitemid 35002070)
38. Gorringe KL, Jacobs S, Thompson ER, et al. High resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications. Clin Cancer Res. 2007;13: 4731-9. (Pubitemid 47294779)
39. Dutt A, Ramos AH, Hammerman PS, et al. Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer. PLoA ONE. 2011;6: e20351.
40. Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med. 2010;2: 62ra93.
41. Edwards J, Krishna NS, Witton CJ, Bartkett JM. Gene amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res. 2003;9: 5271-81. (Pubitemid 37413579)
42. Simon R, Richter J, Wagner U, et al. High-throughput tissue microarray analysis of 3p25 [RAF1] and 8p12 [FGFR1] copy number alterations in urinary bladder cancer. Cancer Res. 2001;61: 4514-9. (Pubitemid 32685782)
43. Yamaguchi F, Saya H, Bruner JM, Morrison RS. Differential expression of 2 fibroblast growth factor receptor genes is associated with malignant progression in human astrocytomas. Proc Natl Acad Sci USA. 1994;91: 484-8. (Pubitemid 24041426)
44. Missiaglia E, Selfe J, Hamdi M, et al. Genomic imbalances in rhadomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: an approach to identify candidate genes involved in tumor development. Genes Chromosom Cancer. 2009;48: 455-67.
45. Kunii K, Davis L, Gorenstein J, et al. FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008;68: 2340-8. (Pubitemid 351521808)
46. Turner N, Lambros MB, Horlings HM, et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene. 2010;29: 2013-23.
47. Azuma K, Tsurutani J, Sakai K, et al. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure. Biochem and Biophys Res Comm. 2011;407: 219-24.
48. Stacey SN, Manolescu P, Sulem P, et al. Common variants on chromosome 5p12 confer susceptibility to estrogen receptorpositive breast cancer. Nat Genet. 2008;40: 704-6.
49. Nord H, Segersten U, Sundgren J, et al. Focal amplifications are associated with high grade and recurrences in stage Ta bladder carcinoma. Int J Cancer. 2009;126: 1390-402. Evidence for the role of FGF amplifications in bladder cancer.
50. Avet-Loiseau H, Facon T, Davier A, et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone de Myelome. Cancer Res. 1999;59: 4546-50. (Pubitemid 29428955)
51. Trudel S, Stewart AK, Rom E, et al. The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t (4;14) multiple myeloma cells. Blood. 2006;107: 4039-46. (Pubitemid 43726812)
52. Yagasaki F, Wakao D, Yokoyama Y, et al. Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t (4;12) (p16;p13) chromosomal translocation. Cancer Res. 2001;61: 8371-4. (Pubitemid 33131107)
53. Sonvilla G, Allersofter S, Heinzle C, et al. Fibroblast growth factor receptor 3-IIIC mediates colorectal cancer growth and migration. Br J Cancer. 2010;102: 1145-56.
54. Van Rhijn BW, Montironi R, Zwarthoff EC, et al. Frequent FGFR3 mutations in urothelial papilloma. J Pathol. 2002;198: 245-51. (Pubitemid 35243883)
55. Rosty C, Aubriot M-H, Cappellen D, et al. Clinical and biological characteristics of cervical neoplasias with FGFR3 mutations. Mol Cancer. 2005;4: 15.
56. Hernandez S, de Muga S, Agell L, et al. FGFR3 mutations in prostate cancer: association with low grade tumors. Mod Pathol. 2009;22: 848-56.
57. di Martino E, L'Hote CG, Kennedy W, et al. Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type-and mutation-specific manner. Oncogene. 2009;28: 4306-16.
58. Dutt A, Salvesen HB, Chen TH, et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci USA. 2008;105: 8713-7. (Pubitemid 351987745)
59. Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dec. 2002;16: 1446-65. (Pubitemid 34686327)
60. Taylor JG, Cheuk AT, Tsang PS, et al. Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. J Clin Invest. 2009;119: 3395-407.
61. Okamoto I, Kaneda H, Satoh T, et al. Phase I safety, pharmacokinetic, and biomarker study of BIBF1120, an oral triple tyrosine kinase inhibitor in patients with advanced solid tumors. Mol Cancer Ther. 2010;9: 2825-33.
62. Mross K, Stefanic M, Gmehling D, et al. Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. Clin Cancer Res. 2010;16: 311-9.
63. du Bois A, Huober J, Stopfer P, et al. A phase I open-label doseescalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies. Ann Oncol. 2010;21: 370-5.
64. Kropff M, Kienast J, Bisping G, et al. An open-label doseescalation study of BIBF 1120 in patients with relapsed or refractory multiple myeloma. Anticancer Res. 2009;29: 4233-8.
65. Lee CP, Attard G, Poupard L, et al. A phase I study of BIBF 1120, an orally active triple angiokinase inhibitor (VEGFR, PDGFR, FGFR) in patients with advanced solid malignancies. J Clin Oncol. 2005;23: 3054.
66. Reck M, Kaiser R, Eschbach C, et al. A phase II double-blind study to investigate efficacy and safety of two doses of the triple angiokinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer. Ann Oncol. 2011;22: 1374-81.
67. Ledermann JA, Hackshaw A, Kaye S, et al. Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol. 2011;29: 3798-804.
68. Bouche O, Maindrault-Goeve F, Ducreux M, et al. Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer. Anticancer Res. 2001;31: 2271-81.
69. Molife R, de Bono JS, Bell S, et al.: A phase II trial to compare BIBF 1120 or BIBW 2992 monotherapy versus a combination of sequential administration of both medications in patients with hormone refractory prostate cancer (HRPC). Presented at the ASCO Genitourinary Cancers Symposium. Orlando FLA, USA; February 26-28, 2009.
70. Sarker D, Molife R, Evans TRJ, et al. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008;14: 2075-81. First published phase I study of a triple angiokinase inhibitor. (Pubitemid 351551118)
71. Kim KB, Chesney J, Robinson D, et al. Phase I/II and pharmacodynamic study of dovotinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma. Clin Cancer Res. 2011;17: 7451-61.
72. Andre F, Baselga J, Ellis MJ, et al. A multicenter, open-label phase II trial of dovotinib, and FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer. Presented at the ASCO Annual Meeting. Chicago ILL, USA; June 3-7, 2011.
73. Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer. 2008;122: 664-71. (Pubitemid 350308963)
74. Yamada K, Yamamoto N, Yamada Y, et al. Phase I dose-escalation study and biomarker analysis of E7080 in patients with advanced solid umors. Cancer Res. 2011;17: 2528-37.
75. Keizer RJ, Gupta A, Mac Gillavry MR, et al. A model of hypertension and proteinuria in cancer patients treated with the antiangiogenic agent E7080. J Pharmacokinet Pharmacodyn. 2010;37: 347-63.
76. Glen H, Boss D, Evans TR, et al. A phase I dose finding study of E7080 in patients (pts) with advanced malignancies. J Clin Oncol, ASCO Annual Meeting Proceedings Part I 25 (18S): 14073.
77. Gild ML, Bullock M, Robinson BG, Clifton-Bligh R. Multikinase inhibitors: a new option for the treatment of thyroid cancer. Nat Rev Endocrinol. 2011;7: 617-24.
78. Huynh H, Ngo VC, Fargnoli J, et al. 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. Clin Cancer Res. 2008;14: 6146-53.
79. Jonker DJ, Rosen LS, Sawyer MB, et al. A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors. Ann Oncol. 2011;22: 1413-9.
80. Park J-W, Finn RS, Kim J-S, et al. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res. 2011;17: 1973-83.
81. Dempke WC, Zippel R. Brivanib, a novel dual VEGF-R2/bFGF-Rinhibitor. Anticancer Res. 2010;30: 4477-83.
82. Haruyasu M, Yutaka U, Shimoyama T, et al. Phase I, pharmacokinetic, and biological studies of TSU-68, a novel multiple receptor tyrosine kinase inhibitor, administered after meals with solid tumors. Cancer Chemother Pharmacol. 2011;67: 1119-28.
83. Ueda Y, Shimoyama T, Murakami H, et al. Phase I and pharmacokinetic study of TSU-68, a novel multiple receptor tyrosine kinase inhibitor, by twice daily oral administration between meals in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2011;67: 1101-9.
84. Kanai F, Yoshida H, Tateishi R, et al. A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2011;67: 315-24.
85. Shin SJ, Jung M, Jeung HC, et al. A phase I pharmacokinetic study of TSU-68 (a multiple tyrosine kinase inhibitor of VEGFR-2, FGF and PDFG) in combination with S-1 and oxaliplatin in metastatic colorectal cancer patients previously treated with chemotherapy. Invest New Drugs 2011, Epub ahead of print: doi: 10.1007/s10637-011-9683-8.
86. Dubreuil P, Letard S, Ciufolini M, et al. Masatanib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One. 2009;4: 37258. doi: 10.1371/journal.pone.0007258.
87. Gavine P, Mooney L, Kilgour E, et al. Characterization of AZD4547: an orally bioavailable, potent and selective inhibitor of FGFR tyrosine kinases 1, 2 and 3. Presented at the 102nd AACR Annual Meeting. Orlando FLA, USA; April 2-6, 2011.
88. Guagnano V, Furet P, Spanka C, et al. 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. J Med Chem. 2011;54: 7066-83.
89. Saxty G, Akkari R, Angibaud P, et al. Fragment based drug discovery of selective inhibitors of fibroblast growth factor receptor (FGFR). Presented at the 102nd AACR Annual Meeting. Orlando FLA, USA; April 2-6, 2011.
90. Trudel S, Stewart AK, Rom E, et al. The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t (4;14) multiple myeloma cells. Blood. 2006;107: 4039-46. (Pubitemid 43726812)
91. Sun HD, Malabunga M, Tonra JR, et al. Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys. Am J Physiol Endocrinol Metab. 2007;292: 964-76.
92. Qing J, Du X, Chen Y, et al. Antibody-based targeting of FGFR3 in bladder carcinoma and t (4;14)-positive multiple myeloma in mice. J Clin Invest. 2009;119: 1216-29.
93. Yap TA, Sandhu SK, Workman P, de Bono JS. Envisioning the future of early anti-cancer drug development. Nat Rev Cancer. 2010;10: 514-23