Genomic aberrations in the FGFR pathway: Opportunities for targeted therapies in solid tumors

Annals of Oncology

Volumn 25, Issue 3, 2014, Pages 552-563

  Dienstmann, R ^a   Rodon, J ^b   Prat, A ^b   Perez Garcia, J ^b   Adamo, B ^b   Felip, E ^b   Cortes, J ^b   Iafrate, A J ^a   Nuciforo, P ^b   Tabernero, J ^b  

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b VALL D HEBRON UNIVERSITY HOSPITAL   (Spain)

Author keywords

Amplification; Cancer; Fibroblast growth factor receptor FGFR; Hyperphosphatemia; Oncogene; Targeted therapy

Indexed keywords

AZD 4547; BGJ 398; DOVITINIB; FIBROBLAST GROWTH FACTOR RECEPTOR; FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 2; JNJ 42756493; LUCITANIB; LY 2874455; MONOCLONAL ANTIBODY; PONATINIB; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; BRAIN TUMOR; BREAST CANCER; CANCER CELL; CELL DEATH; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; COLORECTAL CANCER; CORNEA DISEASE; DIARRHEA; ENDOMETRIUM CANCER; FATIGUE; GENE AMPLIFICATION; GENE MUTATION; GLIOBLASTOMA; HUMAN; HYPERPHOSPHATEMIA; IN SITU HYBRIDIZATION; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL CARCINOMA; LUNG CANCER; LUNG SQUAMOUS CELL CARCINOMA; NAUSEA; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SARCOMA; SOLID TUMOR; STOMACH CANCER; TRANSITIONAL CELL CARCINOMA;

AMPLIFICATION; CANCER; FIBROBLAST GROWTH FACTOR RECEPTOR FGFR; HYPERPHOSPHATEMIA; ONCOGENE; TARGETED THERAPY;

ANTIBODIES, MONOCLONAL; FIBROBLAST GROWTH FACTOR 3; GENE AMPLIFICATION; HUMANS; HYPERPHOSPHATEMIA; MOLECULAR TARGETED THERAPY; NEOPLASMS; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 2; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 3; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 4; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR;

EID: 84896691579     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdt419     Document Type: Review

References (112)

1. Lieu C, Heymach J, Overman M et al. Beyond VEGF: inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin Cancer Res 2011; 17: 6130-6139.
2. Turner N, Grose R. Fibroblast growth factor signaling: from development to cancer. Nature Rev Cancer 2010; 10: 116-129.
3. Crawford Y, Ferrara N. Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies. Trends Pharmacol Sci 2009; 30: 624-630.
4. Knights V, Cook SJ. De-regulated FGF receptors as therapeutic targets in cancer. Pharmacol Ther 2010; 125: 105-117.
5. Wesche J, Haglund K, Haugsten EM. Fibroblast growth factors and their receptors in cancer. Biochem J 2011; 437: 199-213.
6. Heinzle C, Sutterlüty H, Grusch M et al. Targeting fibroblast-growth factor receptor-dependent signaling for cancer therapy. Expert Opin Ther Targets 2011; 5: 829-846.
7. Greulich H, Pollock PM. Targeting mutant fibroblast growth factor receptors in cancer. Trends Mol Med 2011; 17: 283-292.
8. Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res 2012; 18: 1855-1862.
9. Cancer Genome Atlas Network. Comprehensive molecular characterization of human breast tumours. Nature 2012; 490: 61-70.
10. 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: 4360-4367.
11. Reis-Filho JS, Simpson PT, Turner NC et al. FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin Cancer Res 2006; 12: 6652-6662.
12. Brunello E, Brunelli M, Bogina G et al. FGFR-1 amplification in metastatic lymphnodal and haematogenous lobular breast carcinoma. J Exp Clin Cancer Res 2012; 31: 103.
13. Ray ME, Yang ZQ, Albertson D et al. Genomic and expression an analysis of the 8p11-12 amplicon in human breast cancer cell lines. Cancer Res 2004; 64: 40-47.
14. Garcia MJ, Pole JC, Chin SF et al. A 1Mbminimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes. Oncogene 2005; 24: 5235-5245.
15. Haverty PM, Fridlyand J, Li L et al. High-resolution genomic and expression analyses of copy number alterations in breast tumors. Genes Chromosomes Cancer 2008; 47: 530-542.
16. Kwek SS, Roy R, Zhou H et al. Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis. Oncogene 2009; 28: 1892-1903.
17. Fioravanti L, Cappelletti V, Coradini D et al. Int-2 oncogene amplification and prognosis in node-negative breast carcinoma. Int J Cancer 1997; 74: 620-624.
18. Gruel N, Lucchesi C, Raynal V et al. Lobular invasive carcinoma of the breast is a molecular entity distinct from luminal invasive ductal carcinoma. Eur J Cancer 2010; 46: 2399-2407.
19. Turner N, Pearson A, Sharpe R et al. FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res 2010; 70: 2085-2094.
20. Elbauomy Elsheikh S, Green AR, Lambros MB et al. FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res 2007; 9: R23.
21. 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: 2013-2023.
22. Kim S, Dubrovska A, Salamone RJ et al. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells. PLoS One 2013; 8: e51671.
23. Sharpe R, Pearson A, Herrera-Abreu MT et al. FGFR signaling promotes the growth of triple-negative and basal-like breast cancer cell lines both in vitro and in vivo. Clin Cancer Res 2011; 17: 5275-5286.
24. Parker JS, Mullins M, Cheang MC et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009; 27: 1160-1167.
25. 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.
26. Heist RS, Mino-Kenudson M, Sequist LV et al. FGFR1 amplification in squamous cell carcinoma of the lung. J Thorac Oncol 2012; 7: 1775-1780.
27. Schildhaus HU, Heukamp LC, Merkelbach-Bruse S et al. Definition of a fluorescence in-situ hybridization score identifies high-and low-level FGFR1 amplification types in squamous cell lung cancer. Mod Pathol 2012; 25: 1473-1480.
28. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012; 489: 519-525.
29. Kim HR, Kim DJ, Kang DR et al. Fibroblast growth factor receptor 1 gene amplification is associated with poor survival and cigarette smoking dosage in patients with resected squamous cell lung cancer. J Clin Oncol 2013; 31: 731-737.
30. 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: 60-66.
31. von Loga K, Kohlhaussen J, Marx AH et al. FGFR1 amplification is linked to the squamous cell carcinoma subtype in esophageal carcinoma. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR), 6-10 April 2013. Washington DC. Abstr 3024.
32. Zhang J, Zhang L, Su X et al. Translating the therapeutic potential of AZD4547 in FGFR1-amplified non-small cell lung cancer through the use of patient-derived tumor xenograft models. Clin Cancer Res 2012; 18: 6658-6667.
33. Semrad TJ, Mack PC. Fibroblast growth factor signaling in non-small-cell lung cancer. Clin Lung Cancer 2012; 13: 90-95.
34. Marek L, Ware KE, Fritzsche A et al. Fibroblast growth factor (FGF) and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells. Mol Pharmacol 2009; 75: 196-207.
35. Peifer M, Fernández-Cuesta L, Sos ML et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 2012; 44: 1104-1110.
36. Pardo OE, Latigo J, Jeffery RE et al. The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res 2009; 69: 8645-8651.
37. Thomas A, Lee J, Wang Y et al. The role of fibroblast growth factor receptor 1 in small cell lung cancer. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR), 6-10 April 2013. Washington DC. Abstr 5466.
38. Ruotsalainen T, Joensuu H, Mattson K et al. High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer. Cancer Epidemiol Biomarkers Prev 2002; 11: 1492-1495.
39. Matsumoto K, Arao T, Hamaguchi T et al. FGFR2 gene amplification and clinicopathological features in gastric cancer. Br J Cancer 2012; 106: 727-732.
40. Deng N, Goh LK, Wang H et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and cooccurrence among distinct therapeutic targets. Gut 2012; 61: 673-684.
41. 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: 2340-2348.
42. Takeda M, Arao T, Yokote H et al. AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor. Clin Cancer Res 2007; 13: 3051-3057.
43. Gozgit JM, Wong MJ, Moran L et al. Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models. Mol Cancer Ther 2012; 11: 690-699.
44. Guagnano V, Kauffmann A, Wöhrle S et al. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov 2012; 2: 1118-1133.
45. Zhao WM, Wang L, Park H et al. Monoclonal antibodies to fibroblast growth factor receptor 2 effectively inhibit growth of gastric tumor xenografts. Clin Cancer Res 2010; 16: 5750-5758.
46. Bai A, Meetze K, Vo NY et al. GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling. Cancer Res 2010; 70: 7630-7639.
47. Dutt A, Salvesen HB, Chen TH et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci USA 2008; 105: 8713-8717.
48. O'Hara AJ, Bell DW. The genomics and genetics of endometrial cancer. Adv Genomics Genet 2012; 2012: 33-47.
49. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013; 497: 67-73.
50. Yu K, Herr AB, Waksman G et al. Loss of fibroblast growth factor receptor 2 ligand binding specificity in Apert syndrome. Proc Natl Acad Sci USA 2000; 97: 14536-14541.
51. Byron SA, Gartside M, Powell MA et al. FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features. PLoS One 2012; 7: e30801.
52. Cappellen D, De Oliveira C, Ricol D et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 1999; 23: 18-20.
53. Kimura T, Suzuki H, Ohashi T et al. The incidence of thanatophoric dysplasia mutations in FGFR3 gene is higher in low-grade or superficial bladder carcinomas. Cancer 2001; 92: 2555-2561.
54. Billerey C, Chopin D, Aubriot-Lorton MH et al. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 2001; 158: 1955-1959.
55. Tomlinson DC, Baldo O, Harnden P et al. FGFR3 protein expression and its relationship tomutation status and prognostic variables in bladder cancer. J Pathol 2007; 213: 91-98.
56. Al-Ahmadie HA, Iyer G, Janakiraman M et al. Somatic mutation of fibroblast growth factor receptor-3 (FGFR3) defines a distinct morphological subtype of high-grade urothelial carcinoma. J Pathol 2011; 224: 270-279.
57. van Rhijn BW, van der Kwast TH, Liu L et al. The FGFR3 mutation is related to favorable pT1 bladder cancer. J Urol 2012; 187: 310-314.
58. Bernard-Pierrot I, Brams A, Dunois-Lardé C et al. Oncogenic properties of the mutated forms of fibroblast growth factor receptor 3b. Carcinogenesis 2006; 27: 740-747.
59. Jebar AH, Hurst CD, Tomlinson DC et al. FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene 2005; 24: 5218-5225.
60. 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: 1216-1229.
61. Miyake M, Ishii M, Koyama N et al. PD173074, a selective tyrosine kinase inhibitor of FGFR3, inhibits cell proliferation of bladder cancer carrying the FGFR3 gene mutation along with up-regulation of p27/Kip1 and G1/G0 arrest. J Pharmacol Exp Ther 2010; 332: 795-802.
62. Lamont FR, Tomlinson DC, Cooper PA et al. Small molecule FGF receptor inhibitors block FGFR-dependent urothelial carcinoma growth in vitro and in vivo. Br J Cancer 2011; 104: 75-82.
63. Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet 2013; 22: 795-803.
64. Singh D, Chan JM, Zoppoli P et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 2012; 337: 1231-1235.
65. Parker BC, Annala MJ, Cogdell DE et al. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Invest 2013; 123: 855-865.
66. 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: 3395-3407.
67. Zhang K, Chu K, Wu X et al. Amplification of FRS2 and activation of FGFR/FRS2 signaling pathway in high-grade liposarcoma. Cancer Res 2013; 73: 1298-1307.
68. Desnoyers LR, Pai R, Ferrando RE et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene 2008; 27: 85-97.
69. Sawey ET, Chanrion M, Cai C et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening. Cancer Cell 2011; 19: 347-358.
70. Bumbaca D, Wong A, Drake E et al. Highly specific off-target binding identified and eliminated during the humanization of an antibody against FGF receptor 4. MAbs 2011; 3: 376-386.
71. Murphy T, Darby S, Mathers ME et al. Evidence for distinct alterations in the FGF axis in prostate cancer progression to an aggressive clinical phenotype. J Pathol 2010; 220: 452-460.
72. Maruyama-Takahashi K, Shimada N, Imada T et al. A neutralizing anti-fibroblast growth factor (FGF) 8 monoclonal antibody shows anti-tumor activity against FGF8b-expressing LNCaP xenografts in androgen-dependent and-independent conditions. Prostate 2008; 68: 640-650.
73. Feng S, Shao L, Yu W et al. Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression. Clin Cancer Res 2012; 18: 3880-3888.
74. Allen E, Walters I, Hanahan D. Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin Cancer Res 2011; 17: 5299-5310.
75. Kopetz S, HoffPM, 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 2010; 28: 453-459.
76. Batchelor TT, Sorensen 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.
77. Gartside MG, Chen H, Ibrahimi OA et al. Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma. Mol Cancer Res 2009; 7: 41-54.
78. Herrera Abreu M, Garcia-Murilla I, Pearson A et al. functional screens to identify mechanisms of resistance to FGFR inhibitors in FGFR amplified and mutated cell lines. Eur J Cancer 2012; 48(suppl 6): Abstr 163.
79. Gozgit JM, Squillace RM, Wongchenko MJ et al. Combined targeting of FGFR2 and mTOR by ponatinib and ridaforolimus results in synergistic antitumor activity in FGFR2 mutant endometrial cancer models. Cancer Chemother 2013; 71: 1315-1323.
80. Harbinski F, Craig VJ, Sanghavi S et al. Rescue screens with secreted proteins reveal compensatory potential of receptor tyrosine kinases in driving cancer growth. Cancer Discov 2012; 2: 948-959.
81. Issa A, Gill JW, Heideman MR et al. Combinatorial targeting of FGF and ErbB receptors blocks growth and metastatic spread of breast cancer models. Breast Cancer Res 2013; 15: R8.
82. Ware KE, Marshall ME, Heasley LR et al. Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression. PLoS One 2010; 5: e14117.
83. Ye X, Yue P, Patel R et al. Activation of FGFR signaling as a mechanism of acquired resistance to erlotinib in EGFR-mutant lung cancer associated with an EMT. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR), 6-10 April 2013, Washington DC. Abstr 4463.
84. Ware KE, Hinz TK, Kleczko E et al. A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop. Oncogenesis 2013; 2: e39.
85. Terai H, Soejima KN, Yasuda H et al. Activation of the FGF2-FGFR1 autocrine pathway: a novel mechanism of acquired resistance to gefitinib in NSCLC cells. Mol Cancer Res 2013; 11: 759-767.
86. Oliveras-Ferraros C, Cufí S, Queralt B et al. Cross-suppression of EGFR ligands amphiregulin and epiregulin and de-repression of FGFR3 signalling contribute to cetuximab resistance in wild-type KRAS tumour cells. Br J Cancer 2012; 106: 1406-1414.
87. Yadav V, Zhang X, Liu J et al. Reactivation of mitogen-activated protein kinase (MAPK) pathway by FGF receptor 3 (FGFR3)/Ras mediates resistance to vemurafenib in human B-RAF V600E mutant melanoma. J Biol Chem 2012; 287: 28087-28098
88. Brown AP, Courtney CL, King LM et al. Cartilage dysplasia and tissue mineralization in the rat following administration of a FGF receptor tyrosine kinase inhibitor. Toxicol Pathol 2005; 33: 449-455.
89. Dienstmann R, Braña I, Rodon J et al. Toxicity as a biomarker of efficacy of molecular targeted therapies: focus on EGFR and VEGF inhibiting anticancer drugs. Oncologist 2011; 16: 1729-1740.
90. Gavine PR, Mooney L, Kilgour E et al. AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res 2012; 72: 2045-2056.
91. Zhao G, Li WY, Chen D et al. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol Cancer Ther 2011; 10: 2200-2210.
92. Andre F, Bachelot TD, Campone M et al. A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer. J Clin Oncol 2011; 29(Suppl): Abstr 508.
93. Shiang CY, Qi Y, Wang B et al. Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate. Breast Cancer Res Treat 2010; 123: 747-755.
94. Colella G, Damia G, D'Incalci M et al. E-3810 antitumor activity in human xenografts expressing different levels of FGF receptor 1. Cancer Res 2011; 71 (suppl 1): Abstr 595.
95. Konecny GE, Kolarova T, O'Brien NA et al. Activity of the fibroblast growth factor receptor inhibitors dovitinib (TKI258) and NVP-BGJ398 in human endometrial cancer cells. Mol Cancer Ther 2013; 12: 632-642.
96. Okita K, Kumada H, Ikeda K et al. Phase I/II study of E7080 (lenvatinib), a multitargeted tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma: initial assessment of response rate. J Clin Oncol 2012; 30(suppl): Abstr 320.
97. Kim KB, Chesney J, Robinson D et al. Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma. Clin Cancer Res 2011; 17: 7451-7461.
98. Dienstmann R, André F, Soria JC et al. Significant antitumor activity of E-3810, a novel FGFR and VEGFR inhibitor, in patients with FGFR1amplified breast cancer. Ann Oncol 2012; 23(suppl 9): Abstr 3190.
99. Barrios CH, Liu MC, Lee SC et al. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res Treat 2010; 121: 121-131.
100. Moreno-Aspitia A, Morton RF, Hillman DW et al. Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336. J Clin Oncol 2009; 27: 11-15.
101. Wolf J, LoRusso PM, Camidge RD et al. A phase I dose escalation study of NVPBGJ398, a selective pan FGFR inhibitor in genetically preselected advanced solid tumors. In: Proceedings of the103rd Annual Meeting of the American Association for Cancer Research (AACR), 31 March-4 April 2012; Chicago, IL. Abstr LB-122.
102. Andre F, Ranson M, Dean E et al. Results of a phase I study of AZD4547, an inhibitor of fibroblast growth factor receptor, in patients with advanced solid tumors. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research (AACR), 6-10 April 2013, Washington DC. Abstr LB-145.
103. Harding TC, Long L, Palencia S et al. Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer. Sci Transl Med 2013; 5: 178ra39.
104. O'Donnell P, Goldman JW, Gordon MS et al. A phase I dose-escalation study of MFGR1877S, a human monoclonal anti-fibroblast growth factor receptor 3 (FGFR3) antibody, in patients with advanced solid tumors. Eur J Cancer 2012; 48: 191-192. Abstr 621
105. Rodón J, Saura C, Dienstmann R et al. Molecular prescreening to select patient population in early clinical trials. Nat Rev Clin Oncol 2012; 9: 359-366.
106. Dienstmann R, Rodon J, Tabernero J. Biomarker-driven patient selection for early clinical trials. Curr Opin Oncol 2013; 25: 305-312.
107. Zhang J, Wu G, Miller CP et al. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 2013; 45: 602-612.
108. Jones DTW, Hutter B, Jäger N et al. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet 2013; 45: 927-932.
109. Liao RG, Jung J, Tchaicha J et al. Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma. Cancer Res 2013; 73: 5195-5205.
110. Wu YM, Su F, Kalyana-Sundaram S et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov 2013; 3: 636-647.
111. Majewski IJ, Mittempergher L, Davidson NM et al. Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. J Pathol 2013; 230: 270-276.
112. Dieci MV, Arnedos M, Andre F et al. Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives. Cancer Discov 2013; 3: 264-279.