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Erschienen in: Breast Cancer Research 3/2012

01.06.2012 | Review

Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer

verfasst von: Vikram K Jain, Nicholas C Turner

Erschienen in: Breast Cancer Research | Ausgabe 3/2012

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Abstract

Activation of the fibroblast growth factor receptor pathway is a common event in many cancer types. Here we review the role of fibroblast growth factor receptor signalling in breast cancer, from SNPs in FGFR2 that influence breast cancer risk and SNPs in FGFR4 that associate with breast cancer prognosis, and potential therapeutic targets such as receptor amplification and aberrant autocrine and paracrine ligand expression. We discuss the multiple therapeutic strategies in preclinical and clinical development and the current and future challenges to successfully targeting this pathway in cancer.
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Literatur
1.
Zurück zum Zitat Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M: Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study. Clin Cancer Res. 2011, 17: 1147-1159. 10.1158/1078-0432.CCR-10-1869.CrossRefPubMedPubMedCentral Osborne CK, Neven P, Dirix LY, Mackey JR, Robert J, Underhill C, Schiff R, Gutierrez C, Migliaccio I, Anagnostou VK, Rimm DL, Magill P, Sellers M: Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study. Clin Cancer Res. 2011, 17: 1147-1159. 10.1158/1078-0432.CCR-10-1869.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Di Cosimo S, Bendell JC, Cervantes-Ruiperez A, Roda D, Prudkin L, Stein MN, Leighton-Swayze A, Song Y, Ebbinghaus S, Baselga J: A phase I study of the oral mTOR inhibitor ridaforolimus (RIDA) in combination with the IGF-1R antibody dalotozumab (DALO) in patients (pts) with advanced solid tumors [abstract 3008]. J Clin Oncol. 2010, 28 (Suppl): 15s.- Di Cosimo S, Bendell JC, Cervantes-Ruiperez A, Roda D, Prudkin L, Stein MN, Leighton-Swayze A, Song Y, Ebbinghaus S, Baselga J: A phase I study of the oral mTOR inhibitor ridaforolimus (RIDA) in combination with the IGF-1R antibody dalotozumab (DALO) in patients (pts) with advanced solid tumors [abstract 3008]. J Clin Oncol. 2010, 28 (Suppl): 15s.-
3.
Zurück zum Zitat Turner N, Grose R: Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010, 10: 116-129. 10.1038/nrc2780.CrossRefPubMed Turner N, Grose R: Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010, 10: 116-129. 10.1038/nrc2780.CrossRefPubMed
4.
Zurück zum Zitat Kimelman D, Kirschner M: Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell. 1987, 51: 869-877. 10.1016/0092-8674(87)90110-3.CrossRefPubMed Kimelman D, Kirschner M: Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell. 1987, 51: 869-877. 10.1016/0092-8674(87)90110-3.CrossRefPubMed
5.
Zurück zum Zitat De Moerlooze L, Spencer-Dene B, Revest JM, Hajihosseini M, Rosewell I, Dickson C: An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development. 2000, 127: 483-492.PubMed De Moerlooze L, Spencer-Dene B, Revest JM, Hajihosseini M, Rosewell I, Dickson C: An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis. Development. 2000, 127: 483-492.PubMed
7.
Zurück zum Zitat Johnson DE, Williams LT: Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res. 1993, 60: 1-41.CrossRefPubMed Johnson DE, Williams LT: Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res. 1993, 60: 1-41.CrossRefPubMed
8.
Zurück zum Zitat Eswarakumar VP, Lax I, Schlessinger J: Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005, 16: 139-149. 10.1016/j.cytogfr.2005.01.001.CrossRefPubMed Eswarakumar VP, Lax I, Schlessinger J: Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005, 16: 139-149. 10.1016/j.cytogfr.2005.01.001.CrossRefPubMed
9.
Zurück zum Zitat Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, et al: Patterns of somatic mutation in human cancer genomes. Nature. 2007, 446: 153-158. 10.1038/nature05610.CrossRefPubMedPubMedCentral Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, et al: Patterns of somatic mutation in human cancer genomes. Nature. 2007, 446: 153-158. 10.1038/nature05610.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Taylor JGt, Cheuk AT, Tsang PS, Chung JY, Song YK, Desai K, Yu Y, Chen QR, Shah K, Youngblood V, Fang J, Kim SY, Yeung C, Helman LJ, Mendoza A, Ngo V, Staudt LM, Wei JS, Khanna C, Catchpoole D, Qualman SJ, Hewitt SM, Merlino G, Chanock SJ, Khan J: Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. J Clin Invest. 2009, 119: 3395-3407.PubMed Taylor JGt, Cheuk AT, Tsang PS, Chung JY, Song YK, Desai K, Yu Y, Chen QR, Shah K, Youngblood V, Fang J, Kim SY, Yeung C, Helman LJ, Mendoza A, Ngo V, Staudt LM, Wei JS, Khanna C, Catchpoole D, Qualman SJ, Hewitt SM, Merlino G, Chanock SJ, Khan J: Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. J Clin Invest. 2009, 119: 3395-3407.PubMed
11.
Zurück zum Zitat Elbauomy Elsheikh S, Green AR, Lambros MB, Turner NC, Grainge MJ, Powe D, Ellis IO, Reis-Filho JS: FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res. 2007, 9: R23-10.1186/bcr1665.CrossRefPubMedPubMedCentral Elbauomy Elsheikh S, Green AR, Lambros MB, Turner NC, Grainge MJ, Powe D, Ellis IO, Reis-Filho JS: FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res. 2007, 9: R23-10.1186/bcr1665.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Turner N, Pearson A, Sharpe R, Lambros M, Geyer F, Lopez-Garcia MA, Natrajan R, Marchio C, Iorns E, Mackay A, Gillett C, Grigoriadis A, Tutt A, Reis-Filho JS, Ashworth A: FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res. 2010, 70: 2085-2094. 10.1158/0008-5472.CAN-09-3746.CrossRefPubMedPubMedCentral Turner N, Pearson A, Sharpe R, Lambros M, Geyer F, Lopez-Garcia MA, Natrajan R, Marchio C, Iorns E, Mackay A, Gillett C, Grigoriadis A, Tutt A, Reis-Filho JS, Ashworth A: FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res. 2010, 70: 2085-2094. 10.1158/0008-5472.CAN-09-3746.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schottle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansen S, Rauh D, Baessmann I, Altmuller J, Wainer Z, Conron M, Wright G, Russell P, et al: Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med. 2010, 2: 62ra93-10.1126/scitranslmed.3001451.CrossRefPubMedPubMedCentral Weiss J, Sos ML, Seidel D, Peifer M, Zander T, Heuckmann JM, Ullrich RT, Menon R, Maier S, Soltermann A, Moch H, Wagener P, Fischer F, Heynck S, Koker M, Schottle J, Leenders F, Gabler F, Dabow I, Querings S, Heukamp LC, Balke-Want H, Ansen S, Rauh D, Baessmann I, Altmuller J, Wainer Z, Conron M, Wright G, Russell P, et al: Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer. Sci Transl Med. 2010, 2: 62ra93-10.1126/scitranslmed.3001451.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Shackleford GM, MacArthur CA, Kwan HC, Varmus HE: Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 transgenic mice by insertional activation of int-2/Fgf-3 and hst/Fgf-4. Proc Natl Acad Sci USA. 1993, 90: 740-744. 10.1073/pnas.90.2.740.CrossRefPubMedPubMedCentral Shackleford GM, MacArthur CA, Kwan HC, Varmus HE: Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 transgenic mice by insertional activation of int-2/Fgf-3 and hst/Fgf-4. Proc Natl Acad Sci USA. 1993, 90: 740-744. 10.1073/pnas.90.2.740.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Theodorou V, Kimm MA, Boer M, Wessels L, Theelen W, Jonkers J, Hilkens J: MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nat Genet. 2007, 39: 759-769. 10.1038/ng2034.CrossRefPubMed Theodorou V, Kimm MA, Boer M, Wessels L, Theelen W, Jonkers J, Hilkens J: MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nat Genet. 2007, 39: 759-769. 10.1038/ng2034.CrossRefPubMed
16.
Zurück zum Zitat Muller WJ, Lee FS, Dickson C, Peters G, Pattengale P, Leder P: The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J. 1990, 9: 907-913.PubMedPubMedCentral Muller WJ, Lee FS, Dickson C, Peters G, Pattengale P, Leder P: The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J. 1990, 9: 907-913.PubMedPubMedCentral
17.
Zurück zum Zitat Welm BE, Freeman KW, Chen M, Contreras A, Spencer DM, Rosen JM: Inducible dimerization of FGFR1: development of a mouse model to analyze progressive transformation of the mammary gland. J Cell Biol. 2002, 157: 703-714. 10.1083/jcb.200107119.CrossRefPubMedPubMedCentral Welm BE, Freeman KW, Chen M, Contreras A, Spencer DM, Rosen JM: Inducible dimerization of FGFR1: development of a mouse model to analyze progressive transformation of the mammary gland. J Cell Biol. 2002, 157: 703-714. 10.1083/jcb.200107119.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, et al: Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007, 447: 1087-1093. 10.1038/nature05887.CrossRefPubMedPubMedCentral Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, et al: Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007, 447: 1087-1093. 10.1038/nature05887.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF, Hoover RN, Thomas G, Chanock SJ: A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007, 39: 870-874. 10.1038/ng2075.CrossRefPubMedPubMedCentral Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF, Hoover RN, Thomas G, Chanock SJ: A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007, 39: 870-874. 10.1038/ng2075.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Garcia-Closas M, Hall P, Nevanlinna H, Pooley K, Morrison J, Richesson DA, Bojesen SE, Nordestgaard BG, Axelsson CK, Arias JI, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Zamora P, Brauch H, Justenhoven C, Hamann U, Ko YD, Bruening T, Haas S, Dork T, Schurmann P, Hillemanns P, Bogdanova N, Bremer M, Karstens JH, Fagerholm R, Aaltonen K, Aittomaki K, et al: Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 2008, 4: e1000054-10.1371/journal.pgen.1000054.CrossRefPubMedPubMedCentral Garcia-Closas M, Hall P, Nevanlinna H, Pooley K, Morrison J, Richesson DA, Bojesen SE, Nordestgaard BG, Axelsson CK, Arias JI, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Zamora P, Brauch H, Justenhoven C, Hamann U, Ko YD, Bruening T, Haas S, Dork T, Schurmann P, Hillemanns P, Bogdanova N, Bremer M, Karstens JH, Fagerholm R, Aaltonen K, Aittomaki K, et al: Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 2008, 4: e1000054-10.1371/journal.pgen.1000054.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Meyer KB, Maia AT, O'Reilly M, Teschendorff AE, Chin SF, Caldas C, Ponder BA: Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLoS Biol. 2008, 6: e108-10.1371/journal.pbio.0060108.CrossRefPubMedPubMedCentral Meyer KB, Maia AT, O'Reilly M, Teschendorff AE, Chin SF, Caldas C, Ponder BA: Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLoS Biol. 2008, 6: e108-10.1371/journal.pbio.0060108.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Huijts PE, van Dongen M, de Goeij MC, van Moolenbroek AJ, Blanken F, Vreeswijk MP, de Kruijf EM, Mesker WE, van Zwet EW, Tollenaar RA, Smit VT, van Asperen CJ, Devilee P: Allele-specific regulation of FGFR2 expression is cell type-dependent and may increase breast cancer risk through a paracrine stimulus involving FGF10. Breast Cancer Res. 2011, 13: R72-10.1186/bcr2917.CrossRefPubMedPubMedCentral Huijts PE, van Dongen M, de Goeij MC, van Moolenbroek AJ, Blanken F, Vreeswijk MP, de Kruijf EM, Mesker WE, van Zwet EW, Tollenaar RA, Smit VT, van Asperen CJ, Devilee P: Allele-specific regulation of FGFR2 expression is cell type-dependent and may increase breast cancer risk through a paracrine stimulus involving FGF10. Breast Cancer Res. 2011, 13: R72-10.1186/bcr2917.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Jackson D, Bresnick J, Rosewell I, Crafton T, Poulsom R, Stamp G, Dickson C: Fibroblast growth-factor receptor signaling has a role in lobuloalveolar development of the mammary-gland. J Cell Sci. 1997, 110: 1261-1268.PubMed Jackson D, Bresnick J, Rosewell I, Crafton T, Poulsom R, Stamp G, Dickson C: Fibroblast growth-factor receptor signaling has a role in lobuloalveolar development of the mammary-gland. J Cell Sci. 1997, 110: 1261-1268.PubMed
24.
Zurück zum Zitat Bange J, Prechtl D, Cheburkin Y, Specht K, Harbeck N, Schmitt M, Knyazeva T, Muller S, Gartner S, Sures I, Wang H, Imyanitov E, Haring HU, Knayzev P, Iacobelli S, Hofler H, Ullrich A: Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. Cancer Res. 2002, 62: 840-847.PubMed Bange J, Prechtl D, Cheburkin Y, Specht K, Harbeck N, Schmitt M, Knyazeva T, Muller S, Gartner S, Sures I, Wang H, Imyanitov E, Haring HU, Knayzev P, Iacobelli S, Hofler H, Ullrich A: Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. Cancer Res. 2002, 62: 840-847.PubMed
25.
Zurück zum Zitat Spinola M, Leoni V, Pignatiello C, Conti B, Ravagnani F, Pastorino U, Dragani TA: Functional FGFR4 Gly388Arg polymorphism predicts prognosis in lung adenocarcinoma patients. J Clin Oncol. 2005, 23: 7307-7311. 10.1200/JCO.2005.17.350.CrossRefPubMed Spinola M, Leoni V, Pignatiello C, Conti B, Ravagnani F, Pastorino U, Dragani TA: Functional FGFR4 Gly388Arg polymorphism predicts prognosis in lung adenocarcinoma patients. J Clin Oncol. 2005, 23: 7307-7311. 10.1200/JCO.2005.17.350.CrossRefPubMed
26.
Zurück zum Zitat Spinola M, Leoni VP, Tanuma J, Pettinicchio A, Frattini M, Signoroni S, Agresti R, Giovanazzi R, Pilotti S, Bertario L, Ravagnani F, Dragani TA: FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer. Oncol Rep. 2005, 14: 415-419.PubMed Spinola M, Leoni VP, Tanuma J, Pettinicchio A, Frattini M, Signoroni S, Agresti R, Giovanazzi R, Pilotti S, Bertario L, Ravagnani F, Dragani TA: FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer. Oncol Rep. 2005, 14: 415-419.PubMed
27.
Zurück zum Zitat Thussbas C, Nahrig J, Streit S, Bange J, Kriner M, Kates R, Ulm K, Kiechle M, Hoefler H, Ullrich A, Harbeck N: FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. J Clin Oncol. 2006, 24: 3747-3755. 10.1200/JCO.2005.04.8587.CrossRefPubMed Thussbas C, Nahrig J, Streit S, Bange J, Kriner M, Kates R, Ulm K, Kiechle M, Hoefler H, Ullrich A, Harbeck N: FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. J Clin Oncol. 2006, 24: 3747-3755. 10.1200/JCO.2005.04.8587.CrossRefPubMed
28.
Zurück zum Zitat Sugiyama N, Varjosalo M, Meller P, Lohi J, Hyytiainen M, Kilpinen S, Kallioniemi O, Ingvarsen S, Engelholm LH, Taipale J, Alitalo K, Keski-Oja J, Lehti K: Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation. Cancer Res. 2010, 70: 7851-7861. 10.1158/0008-5472.CAN-10-1223.CrossRefPubMed Sugiyama N, Varjosalo M, Meller P, Lohi J, Hyytiainen M, Kilpinen S, Kallioniemi O, Ingvarsen S, Engelholm LH, Taipale J, Alitalo K, Keski-Oja J, Lehti K: Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation. Cancer Res. 2010, 70: 7851-7861. 10.1158/0008-5472.CAN-10-1223.CrossRefPubMed
29.
Zurück zum Zitat Wang J, Yu W, Cai Y, Ren C, Ittmann MM: Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression. Neoplasia. 2008, 10: 847-856.CrossRefPubMedPubMedCentral Wang J, Yu W, Cai Y, Ren C, Ittmann MM: Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression. Neoplasia. 2008, 10: 847-856.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Sugiyama N, Varjosalo M, Meller P, Lohi J, Chan KM, Zhou Z, Alitalo K, Taipale J, Keski-Oja J, Lehti K: FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase-FGFR4 complex. Proc Natl Acad Sci USA. 2010, 107: 15786-15791. 10.1073/pnas.0914459107.CrossRefPubMedPubMedCentral Sugiyama N, Varjosalo M, Meller P, Lohi J, Chan KM, Zhou Z, Alitalo K, Taipale J, Keski-Oja J, Lehti K: FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type 1 matrix metalloproteinase-FGFR4 complex. Proc Natl Acad Sci USA. 2010, 107: 15786-15791. 10.1073/pnas.0914459107.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Seitzer N, Mayr T, Streit S, Ullrich A: A single nucleotide change in the mouse genome accelerates breast cancer progression. Cancer Res. 2010, 70: 802-812. 10.1158/0008-5472.CAN-09-3239.CrossRefPubMed Seitzer N, Mayr T, Streit S, Ullrich A: A single nucleotide change in the mouse genome accelerates breast cancer progression. Cancer Res. 2010, 70: 802-812. 10.1158/0008-5472.CAN-09-3239.CrossRefPubMed
32.
Zurück zum Zitat Marme F, Werft W, Benner A, Burwinkel B, Sinn P, Sohn C, Lichter P, Hahn M, Schneeweiss A: FGFR4 Arg388 genotype is associated with pathological complete response to neoadjuvant chemotherapy for primary breast cancer. Ann Oncol. 2010, 21: 1636-1642. 10.1093/annonc/mdq017.CrossRefPubMed Marme F, Werft W, Benner A, Burwinkel B, Sinn P, Sohn C, Lichter P, Hahn M, Schneeweiss A: FGFR4 Arg388 genotype is associated with pathological complete response to neoadjuvant chemotherapy for primary breast cancer. Ann Oncol. 2010, 21: 1636-1642. 10.1093/annonc/mdq017.CrossRefPubMed
33.
Zurück zum Zitat Turner N, Lambros MB, Horlings HM, Pearson A, Sharpe R, Natrajan R, Geyer FC, van Kouwenhove M, Kreike B, Mackay A, Ashworth A, van de Vijver MJ, Reis-Filho JS: Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene. 2010, 29: 2013-2023. 10.1038/onc.2009.489.CrossRefPubMedPubMedCentral Turner N, Lambros MB, Horlings HM, Pearson A, Sharpe R, Natrajan R, Geyer FC, van Kouwenhove M, Kreike B, Mackay A, Ashworth A, van de Vijver MJ, Reis-Filho JS: Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene. 2010, 29: 2013-2023. 10.1038/onc.2009.489.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Tannheimer SL, Rehemtulla A, Ethier SP: Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE. Breast Cancer Res. 2000, 2: 311-320. 10.1186/bcr73.CrossRefPubMedPubMedCentral Tannheimer SL, Rehemtulla A, Ethier SP: Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE. Breast Cancer Res. 2000, 2: 311-320. 10.1186/bcr73.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Bai A, Meetze K, Vo NY, Kollipara S, Mazsa EK, Winston WM, Weiler S, Poling LL, Chen T, Ismail NS, Jiang J, Lerner L, Gyuris J, Weng Z: GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling. Cancer Res. 2010, 70: 7630-7639. 10.1158/0008-5472.CAN-10-1489.CrossRefPubMed Bai A, Meetze K, Vo NY, Kollipara S, Mazsa EK, Winston WM, Weiler S, Poling LL, Chen T, Ismail NS, Jiang J, Lerner L, Gyuris J, Weng Z: GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling. Cancer Res. 2010, 70: 7630-7639. 10.1158/0008-5472.CAN-10-1489.CrossRefPubMed
36.
Zurück zum Zitat Cha JY, Maddileti S, Mitin N, Harden TK, Der CJ: Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J Biol Chem. 2009, 284: 6227-6240.CrossRefPubMedPubMedCentral Cha JY, Maddileti S, Mitin N, Harden TK, Der CJ: Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J Biol Chem. 2009, 284: 6227-6240.CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Heiskanen M, Kononen J, Barlund M, Torhorst J, Sauter G, Kallioniemi A, Kallioniemi O: CGH, cDNA and tissue microarray analyses implicate FGFR2 amplification in a small subset of breast tumors. Anal Cell Pathol. 2001, 22: 229-234.CrossRefPubMedPubMedCentral Heiskanen M, Kononen J, Barlund M, Torhorst J, Sauter G, Kallioniemi A, Kallioniemi O: CGH, cDNA and tissue microarray analyses implicate FGFR2 amplification in a small subset of breast tumors. Anal Cell Pathol. 2001, 22: 229-234.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Kunii K, Davis L, Gorenstein J, Hatch H, Yashiro M, Di Bacco A, Elbi C, Lutterbach B: FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008, 68: 2340-2348. 10.1158/0008-5472.CAN-07-5229.CrossRefPubMed Kunii K, Davis L, Gorenstein J, Hatch H, Yashiro M, Di Bacco A, Elbi C, Lutterbach B: FGFR2-amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res. 2008, 68: 2340-2348. 10.1158/0008-5472.CAN-07-5229.CrossRefPubMed
39.
Zurück zum Zitat Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, McHenry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, et al: The landscape of somatic copy-number alteration across human cancers. Nature. 2010, 463: 899-905. 10.1038/nature08822.CrossRefPubMedPubMedCentral Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, McHenry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, et al: The landscape of somatic copy-number alteration across human cancers. Nature. 2010, 463: 899-905. 10.1038/nature08822.CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R, Rodriguez C, Theillet C: Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 1997, 57: 4360-4367.PubMed Courjal F, Cuny M, Simony-Lafontaine J, Louason G, Speiser P, Zeillinger R, Rodriguez C, Theillet C: Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 1997, 57: 4360-4367.PubMed
41.
Zurück zum Zitat Gelsi-Boyer V, Orsetti B, Cervera N, Finetti P, Sircoulomb F, Rouge C, Lasorsa L, Letessier A, Ginestier C, Monville F, Esteyries S, Adelaide J, Esterni B, Henry C, Ethier SP, Bibeau F, Mozziconacci MJ, Charafe-Jauffret E, Jacquemier J, Bertucci F, Birnbaum D, Theillet C, Chaffanet M: Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. 2005, 3: 655-667. 10.1158/1541-7786.MCR-05-0128.CrossRefPubMed Gelsi-Boyer V, Orsetti B, Cervera N, Finetti P, Sircoulomb F, Rouge C, Lasorsa L, Letessier A, Ginestier C, Monville F, Esteyries S, Adelaide J, Esterni B, Henry C, Ethier SP, Bibeau F, Mozziconacci MJ, Charafe-Jauffret E, Jacquemier J, Bertucci F, Birnbaum D, Theillet C, Chaffanet M: Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. 2005, 3: 655-667. 10.1158/1541-7786.MCR-05-0128.CrossRefPubMed
42.
Zurück zum Zitat Letessier A, Sircoulomb F, Ginestier C, Cervera N, Monville F, Gelsi-Boyer V, Esterni B, Geneix J, Finetti P, Zemmour C, Viens P, Charafe-Jauffret E, Jacquemier J, Birnbaum D, Chaffanet M: Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers. BMC Cancer. 2006, 6: 245-10.1186/1471-2407-6-245.CrossRefPubMedPubMedCentral Letessier A, Sircoulomb F, Ginestier C, Cervera N, Monville F, Gelsi-Boyer V, Esterni B, Geneix J, Finetti P, Zemmour C, Viens P, Charafe-Jauffret E, Jacquemier J, Birnbaum D, Chaffanet M: Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers. BMC Cancer. 2006, 6: 245-10.1186/1471-2407-6-245.CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Reis-Filho JS, Simpson PT, Turner NC, Lambros MB, Jones C, Mackay A, Grigoriadis A, Sarrio D, Savage K, Dexter T, Iravani M, Fenwick K, Weber B, Hardisson D, Schmitt FC, Palacios J, Lakhani SR, Ashworth A: FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin Cancer Res. 2006, 12: 6652-6662. 10.1158/1078-0432.CCR-06-1164.CrossRefPubMed Reis-Filho JS, Simpson PT, Turner NC, Lambros MB, Jones C, Mackay A, Grigoriadis A, Sarrio D, Savage K, Dexter T, Iravani M, Fenwick K, Weber B, Hardisson D, Schmitt FC, Palacios J, Lakhani SR, Ashworth A: FGFR1 emerges as a potential therapeutic target for lobular breast carcinomas. Clin Cancer Res. 2006, 12: 6652-6662. 10.1158/1078-0432.CCR-06-1164.CrossRefPubMed
44.
Zurück zum Zitat Jacquemier J, Adelaide J, Parc P, Penault-Llorca F, Planche J, deLapeyriere O, Birnbaum D: Expression of the FGFR1 gene in human breast-carcinoma cells. Int J Cancer. 1994, 59: 373-378. 10.1002/ijc.2910590314.CrossRefPubMed Jacquemier J, Adelaide J, Parc P, Penault-Llorca F, Planche J, deLapeyriere O, Birnbaum D: Expression of the FGFR1 gene in human breast-carcinoma cells. Int J Cancer. 1994, 59: 373-378. 10.1002/ijc.2910590314.CrossRefPubMed
45.
Zurück zum Zitat Holland DG, Burleigh A, Git A, Goldgraben MA, Perez-Mancera PA, Chin SF, Hurtado A, Bruna A, Ali HR, Greenwood W, Dunning MJ, Samarajiwa S, Menon S, Rueda OM, Lynch AG, McKinney S, Ellis IO, Eaves CJ, Carroll JS, Curtis C, Aparicio S, Caldas C: ZNF703 is a common luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med. 2011, 3: 167-180. 10.1002/emmm.201100122.CrossRefPubMedPubMedCentral Holland DG, Burleigh A, Git A, Goldgraben MA, Perez-Mancera PA, Chin SF, Hurtado A, Bruna A, Ali HR, Greenwood W, Dunning MJ, Samarajiwa S, Menon S, Rueda OM, Lynch AG, McKinney S, Ellis IO, Eaves CJ, Carroll JS, Curtis C, Aparicio S, Caldas C: ZNF703 is a common luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med. 2011, 3: 167-180. 10.1002/emmm.201100122.CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Sircoulomb F, Nicolas N, Ferrari A, Finetti P, Bekhouche I, Rousselet E, Lonigro A, Adelaide J, Baudelet E, Esteyries S, Wicinski J, Audebert S, Charafe-Jauffret E, Jacquemier J, Lopez M, Borg JP, Sotiriou C, Popovici C, Bertucci F, Birnbaum D, Chaffanet M, Ginestier C: ZNF703 gene amplification at 8p12 specifies luminal B breast cancer. EMBO Mol Med. 2011, 3: 153-166. 10.1002/emmm.201100121.CrossRefPubMedPubMedCentral Sircoulomb F, Nicolas N, Ferrari A, Finetti P, Bekhouche I, Rousselet E, Lonigro A, Adelaide J, Baudelet E, Esteyries S, Wicinski J, Audebert S, Charafe-Jauffret E, Jacquemier J, Lopez M, Borg JP, Sotiriou C, Popovici C, Bertucci F, Birnbaum D, Chaffanet M, Ginestier C: ZNF703 gene amplification at 8p12 specifies luminal B breast cancer. EMBO Mol Med. 2011, 3: 153-166. 10.1002/emmm.201100121.CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Bernard-Pierrot I, Gruel N, Stransky N, Vincent-Salomon A, Reyal F, Raynal V, Vallot C, Pierron G, Radvanyi F, Delattre O: Characterization of the recurrent 8p11-12 amplicon identifies PPAPDC1B, a phosphatase protein, as a new therapeutic target in breast cancer. Cancer Res. 2008, 68: 7165-7175. 10.1158/0008-5472.CAN-08-1360.CrossRefPubMed Bernard-Pierrot I, Gruel N, Stransky N, Vincent-Salomon A, Reyal F, Raynal V, Vallot C, Pierron G, Radvanyi F, Delattre O: Characterization of the recurrent 8p11-12 amplicon identifies PPAPDC1B, a phosphatase protein, as a new therapeutic target in breast cancer. Cancer Res. 2008, 68: 7165-7175. 10.1158/0008-5472.CAN-08-1360.CrossRefPubMed
48.
Zurück zum Zitat Sharpe R, Pearson A, Herrera-Abreu MT, Johnson D, Mackay A, Welti JC, Natrajan R, Reynolds AR, Reis-Filho JS, Ashworth A, Turner NC: 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. 10.1158/1078-0432.CCR-10-2727.CrossRefPubMedPubMedCentral Sharpe R, Pearson A, Herrera-Abreu MT, Johnson D, Mackay A, Welti JC, Natrajan R, Reynolds AR, Reis-Filho JS, Ashworth A, Turner NC: 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. 10.1158/1078-0432.CCR-10-2727.CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat Xian W, Pappas L, Pandya D, Selfors LM, Derksen PW, de Bruin M, Gray NS, Jonkers J, Rosen JM, Brugge JS: Fibroblast growth factor receptor 1-transformed mammary epithelial cells are dependent on RSK activity for growth and survival. Cancer Res. 2009, 69: 2244-2251. 10.1158/0008-5472.CAN-08-3398.CrossRefPubMed Xian W, Pappas L, Pandya D, Selfors LM, Derksen PW, de Bruin M, Gray NS, Jonkers J, Rosen JM, Brugge JS: Fibroblast growth factor receptor 1-transformed mammary epithelial cells are dependent on RSK activity for growth and survival. Cancer Res. 2009, 69: 2244-2251. 10.1158/0008-5472.CAN-08-3398.CrossRefPubMed
50.
Zurück zum Zitat Pond AC, Herschkowitz JI, Schwertfeger KL, Welm B, Zhang Y, York B, Cardiff RD, Hilsenbeck S, Perou CM, Creighton CJ, Lloyd RE, Rosen JM: Fibroblast growth factor receptor signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-Wnt-1 mouse model of breast cancer. Cancer Res. 2010, 70: 4868-4879. 10.1158/0008-5472.CAN-09-4404.CrossRefPubMedPubMedCentral Pond AC, Herschkowitz JI, Schwertfeger KL, Welm B, Zhang Y, York B, Cardiff RD, Hilsenbeck S, Perou CM, Creighton CJ, Lloyd RE, Rosen JM: Fibroblast growth factor receptor signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-Wnt-1 mouse model of breast cancer. Cancer Res. 2010, 70: 4868-4879. 10.1158/0008-5472.CAN-09-4404.CrossRefPubMedPubMedCentral
51.
Zurück zum Zitat Bade LK, Goldberg JE, Dehut HA, Hall MK, Schwertfeger KL: Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor. J Cell Sci. 2011, 124 (Pt 18): 3106-3117.CrossRefPubMedPubMedCentral Bade LK, Goldberg JE, Dehut HA, Hall MK, Schwertfeger KL: Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor. J Cell Sci. 2011, 124 (Pt 18): 3106-3117.CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Kang S, Dong S, Gu TL, Guo A, Cohen MS, Lonial S, Khoury HJ, Fabbro D, Gilliland DG, Bergsagel PL, Taunton J, Polakiewicz RD, Chen J: FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway. Cancer Cell. 2007, 12: 201-214. 10.1016/j.ccr.2007.08.003.CrossRefPubMedPubMedCentral Kang S, Dong S, Gu TL, Guo A, Cohen MS, Lonial S, Khoury HJ, Fabbro D, Gilliland DG, Bergsagel PL, Taunton J, Polakiewicz RD, Chen J: FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway. Cancer Cell. 2007, 12: 201-214. 10.1016/j.ccr.2007.08.003.CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Kwek SS, Roy R, Zhou H, Climent J, Martinez-Climent JA, Fridlyand J, Albertson DG: Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis. Oncogene. 2009, 28: 1892-1903. 10.1038/onc.2009.34.CrossRefPubMedPubMedCentral Kwek SS, Roy R, Zhou H, Climent J, Martinez-Climent JA, Fridlyand J, Albertson DG: Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis. Oncogene. 2009, 28: 1892-1903. 10.1038/onc.2009.34.CrossRefPubMedPubMedCentral
54.
Zurück zum Zitat Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, Nicoletti R, Winckler W, Grewal R, Hanna M, Wyhs N, Ziaugra L, Richter DJ, Trovik J, Engelsen IB, Stefansson IM, Fennell T, Cibulskis K, Zody MC, Akslen LA, Gabriel S, Wong KK, Sellers WR, Meyerson M, Greulich H: Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci USA. 2008, 105: 8713-8717. 10.1073/pnas.0803379105.CrossRefPubMedPubMedCentral Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, Nicoletti R, Winckler W, Grewal R, Hanna M, Wyhs N, Ziaugra L, Richter DJ, Trovik J, Engelsen IB, Stefansson IM, Fennell T, Cibulskis K, Zody MC, Akslen LA, Gabriel S, Wong KK, Sellers WR, Meyerson M, Greulich H: Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc Natl Acad Sci USA. 2008, 105: 8713-8717. 10.1073/pnas.0803379105.CrossRefPubMedPubMedCentral
55.
Zurück zum Zitat Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F: Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 1999, 23: 18-20.PubMed Cappellen D, De Oliveira C, Ricol D, de Medina S, Bourdin J, Sastre-Garau X, Chopin D, Thiery JP, Radvanyi F: Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 1999, 23: 18-20.PubMed
56.
Zurück zum Zitat Relf M, LeJeune S, Scott PA, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL: Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res. 1997, 57: 963-969.PubMed Relf M, LeJeune S, Scott PA, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL: Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res. 1997, 57: 963-969.PubMed
57.
Zurück zum Zitat Liu Y, Wang JL, Chang H, Barsky SH, Nguyen M: Breast-cancer diagnosis with nipple fluid bFGF. Lancet. 2000, 356: 567-10.1016/S0140-6736(00)02587-3.CrossRefPubMed Liu Y, Wang JL, Chang H, Barsky SH, Nguyen M: Breast-cancer diagnosis with nipple fluid bFGF. Lancet. 2000, 356: 567-10.1016/S0140-6736(00)02587-3.CrossRefPubMed
58.
Zurück zum Zitat Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D: Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987, 325: 257-259. 10.1038/325257a0.CrossRefPubMed Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D: Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987, 325: 257-259. 10.1038/325257a0.CrossRefPubMed
59.
Zurück zum Zitat Welti JC, Gourlaouen M, Powles T, Kudahetti SC, Wilson P, Berney DM, Reynolds AR: Fibroblast growth factor 2 regulates endothelial cell sensitivity to sunitinib. Oncogene. 2011, 30: 1183-1193. 10.1038/onc.2010.503.CrossRefPubMed Welti JC, Gourlaouen M, Powles T, Kudahetti SC, Wilson P, Berney DM, Reynolds AR: Fibroblast growth factor 2 regulates endothelial cell sensitivity to sunitinib. Oncogene. 2011, 30: 1183-1193. 10.1038/onc.2010.503.CrossRefPubMed
60.
Zurück zum Zitat Fillmore CM, Gupta PB, Rudnick JA, Caballero S, Keller PJ, Lander ES, Kuperwasser C: Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci USA. 2010, 107: 21737-21742. 10.1073/pnas.1007863107.CrossRefPubMedPubMedCentral Fillmore CM, Gupta PB, Rudnick JA, Caballero S, Keller PJ, Lander ES, Kuperwasser C: Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci USA. 2010, 107: 21737-21742. 10.1073/pnas.1007863107.CrossRefPubMedPubMedCentral
61.
Zurück zum Zitat Qing J, Du X, Chen Y, Chan P, Li H, Wu P, Marsters S, Stawicki S, Tien J, Totpal K, Ross S, Stinson S, Dornan D, French D, Wang QR, Stephan JP, Wu Y, Wiesmann C, Ashkenazi A: Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice. J Clin Invest. 2009, 119: 1216-1229. 10.1172/JCI38017.CrossRefPubMedPubMedCentral Qing J, Du X, Chen Y, Chan P, Li H, Wu P, Marsters S, Stawicki S, Tien J, Totpal K, Ross S, Stinson S, Dornan D, French D, Wang QR, Stephan JP, Wu Y, Wiesmann C, Ashkenazi A: Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice. J Clin Invest. 2009, 119: 1216-1229. 10.1172/JCI38017.CrossRefPubMedPubMedCentral
62.
Zurück zum Zitat Sun HD, Malabunga M, Tonra JR, DiRenzo R, Carrick FE, Zheng H, Berthoud HR, McGuinness OP, Shen J, Bohlen P, Leibel RL, Kussie P: 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: E964-E976.CrossRefPubMed Sun HD, Malabunga M, Tonra JR, DiRenzo R, Carrick FE, Zheng H, Berthoud HR, McGuinness OP, Shen J, Bohlen P, Leibel RL, Kussie P: 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: E964-E976.CrossRefPubMed
63.
Zurück zum Zitat Marshall ME, Hinz TK, Kono SA, Singleton KR, Bichon B, Ware KE, Marek L, Frederick BA, Raben D, Heasley LE: Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2011, 17: 5016-5025. 10.1158/1078-0432.CCR-11-0050.CrossRefPubMedPubMedCentral Marshall ME, Hinz TK, Kono SA, Singleton KR, Bichon B, Ware KE, Marek L, Frederick BA, Raben D, Heasley LE: Fibroblast growth factor receptors are components of autocrine signaling networks in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2011, 17: 5016-5025. 10.1158/1078-0432.CCR-11-0050.CrossRefPubMedPubMedCentral
64.
Zurück zum Zitat Andre F, Bachelot TD, Campone M, Dalenc F, Perez-Garcia JM, Hurvitz SA, Turner NC, Rugo HS, Shi MM, Zhang Y, Kay ACM, Yovine AJ, Baselga J: A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer [abstract 508]. J Clin Oncol. 2011, 29 (Suppl): Andre F, Bachelot TD, Campone M, Dalenc F, Perez-Garcia JM, Hurvitz SA, Turner NC, Rugo HS, Shi MM, Zhang Y, Kay ACM, Yovine AJ, Baselga J: A multicenter, open-label phase II trial of dovitinib, an FGFR1 inhibitor, in FGFR1 amplified and non-amplified metastatic breast cancer [abstract 508]. J Clin Oncol. 2011, 29 (Suppl):
65.
Zurück zum Zitat Tashiro E, Maruki H, Minato Y, Doki Y, Weinstein IB, Imoto M: Overexpression of cyclin D1 contributes to malignancy by up-regulation of fibroblast growth factor receptor 1 via the pRB/E2F pathway. Cancer Res. 2003, 63: 424-431.PubMed Tashiro E, Maruki H, Minato Y, Doki Y, Weinstein IB, Imoto M: Overexpression of cyclin D1 contributes to malignancy by up-regulation of fibroblast growth factor receptor 1 via the pRB/E2F pathway. Cancer Res. 2003, 63: 424-431.PubMed
66.
Zurück zum Zitat Soria JC, Dienstmann R, de Braud F, Cereda R, Bahleda R, Hollebecque A, Tabernero J, Delmonte A, Dromain C, Lassau N , Farace F, Zucchetti M, Marsoni S, Camboni MG: First-In-Man study of E-3810, a novel VEGFR and FGFR inhibitor, in patients with advanced solid tumors. Annals Oncol. 2012, 23 (Suppl 1): i15-i25.CrossRef Soria JC, Dienstmann R, de Braud F, Cereda R, Bahleda R, Hollebecque A, Tabernero J, Delmonte A, Dromain C, Lassau N , Farace F, Zucchetti M, Marsoni S, Camboni MG: First-In-Man study of E-3810, a novel VEGFR and FGFR inhibitor, in patients with advanced solid tumors. Annals Oncol. 2012, 23 (Suppl 1): i15-i25.CrossRef
67.
Zurück zum Zitat Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ: Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010, 363: 1693-1703. 10.1056/NEJMoa1006448.CrossRefPubMedPubMedCentral Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Janne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ: Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010, 363: 1693-1703. 10.1056/NEJMoa1006448.CrossRefPubMedPubMedCentral
68.
Zurück zum Zitat Freier K, Schwaenen C, Sticht C, Flechtenmacher C, Muhling J, Hofele C, Radlwimmer B, Lichter P, Joos S: Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol. 2007, 43: 60-66. 10.1016/j.oraloncology.2006.01.005.CrossRefPubMed Freier K, Schwaenen C, Sticht C, Flechtenmacher C, Muhling J, Hofele C, Radlwimmer B, Lichter P, Joos S: Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol. 2007, 43: 60-66. 10.1016/j.oraloncology.2006.01.005.CrossRefPubMed
69.
Zurück zum Zitat Wohrle S, Bonny O, Beluch N, Gaulis S, Stamm C, Scheibler M, Muller M, Kinzel B, Thuery A, Brueggen J, Hynes NE, Sellers WR, Hofmann F, Graus-Porta D: FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone. J Bone Miner Res. 2011, 26: 2486-2497. 10.1002/jbmr.478.CrossRefPubMed Wohrle S, Bonny O, Beluch N, Gaulis S, Stamm C, Scheibler M, Muller M, Kinzel B, Thuery A, Brueggen J, Hynes NE, Sellers WR, Hofmann F, Graus-Porta D: FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone. J Bone Miner Res. 2011, 26: 2486-2497. 10.1002/jbmr.478.CrossRefPubMed
70.
Zurück zum Zitat Baselga J, Campone M, Piccart M, Burris HA, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012, 366: 520-529. 10.1056/NEJMoa1109653.CrossRefPubMed Baselga J, Campone M, Piccart M, Burris HA, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012, 366: 520-529. 10.1056/NEJMoa1109653.CrossRefPubMed
71.
Zurück zum Zitat Ratain MJ, Schwartz GK, Oza AM, Rudin CM, Kaye SB, De Jonge MJ, Khayat D, Awada A, Sawyer MB, Obel JC, Medioni J, Evans TRJ, De Greve J, Soetekouw PM, Baurain J, O'Dwyer PJ, Hartman C, Poulart V, Walters IB: Brivanib (BMS-582664) in advanced solid tumors (AST): results of a phase II randomized discontinuation trial (RDT) [abstract 3079]. J Clin Oncol. 2011, 29 (Suppl): Ratain MJ, Schwartz GK, Oza AM, Rudin CM, Kaye SB, De Jonge MJ, Khayat D, Awada A, Sawyer MB, Obel JC, Medioni J, Evans TRJ, De Greve J, Soetekouw PM, Baurain J, O'Dwyer PJ, Hartman C, Poulart V, Walters IB: Brivanib (BMS-582664) in advanced solid tumors (AST): results of a phase II randomized discontinuation trial (RDT) [abstract 3079]. J Clin Oncol. 2011, 29 (Suppl):
72.
Zurück zum Zitat Bouché O, Ducreux M, Lledo G, André T, Maindrault-Goebel F, Stopfer P, Oum'Hamed Z, Chadjaa M, de Gramont A: A phase II trial of weekly alternating sequential administration of BIBF1120 and BIBW2992 in patients with advanced colorectal cancer [abstract 15001]. J Clin Oncol. 2008, 26 (Suppl): Bouché O, Ducreux M, Lledo G, André T, Maindrault-Goebel F, Stopfer P, Oum'Hamed Z, Chadjaa M, de Gramont A: A phase II trial of weekly alternating sequential administration of BIBF1120 and BIBW2992 in patients with advanced colorectal cancer [abstract 15001]. J Clin Oncol. 2008, 26 (Suppl):
73.
Zurück zum Zitat Talpaz M, Shah NP, Deininger MW, Mauro MJ, Flinn IW, Lustgarten S, Lindmark W, Gozgit JM, Clackson T, Turner CD, Haluska FG, Kantarjian H, Cortes JE: Ponatinib in patients with acute myeloid leukemia (AML): preliminary findings from a phase I study in hematologic malignancies [abstract 6518]. J Clin Oncol. 2011, 29 (Suppl): Talpaz M, Shah NP, Deininger MW, Mauro MJ, Flinn IW, Lustgarten S, Lindmark W, Gozgit JM, Clackson T, Turner CD, Haluska FG, Kantarjian H, Cortes JE: Ponatinib in patients with acute myeloid leukemia (AML): preliminary findings from a phase I study in hematologic malignancies [abstract 6518]. J Clin Oncol. 2011, 29 (Suppl):
76.
Zurück zum Zitat Xu J, Wang Y, Ye CY, Huang C, Zhang XH, Sai Y, Shen L, MU H: Phase I study on safety and pharmacokinetics of sulfatinib, a selective VEGFR/FGFR dual inhibitor, in Chinese patients with advanced solid tumors [abstract e13558]. J Clin Oncol. 2011, 29 (Suppl): Xu J, Wang Y, Ye CY, Huang C, Zhang XH, Sai Y, Shen L, MU H: Phase I study on safety and pharmacokinetics of sulfatinib, a selective VEGFR/FGFR dual inhibitor, in Chinese patients with advanced solid tumors [abstract e13558]. J Clin Oncol. 2011, 29 (Suppl):
77.
Zurück zum Zitat Xie L, Su X, Zhang D, Tang L, Xu J, Wang M, Yin L, Zhang J, Ye K, Wang Z, Kilgour E, Qunsheng J: AZD4547, a potent and selective inhibitor of FGF-receptor tyrosine kinases 1, 2 and 3, inhibits the growth of FGF-receptor 2 driven gastric cancer models in vitro and in vivo [abstract 1643]. Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2-6 April 2011; Orlando, FL. 2011, Philadelphia, PA: AACR Xie L, Su X, Zhang D, Tang L, Xu J, Wang M, Yin L, Zhang J, Ye K, Wang Z, Kilgour E, Qunsheng J: AZD4547, a potent and selective inhibitor of FGF-receptor tyrosine kinases 1, 2 and 3, inhibits the growth of FGF-receptor 2 driven gastric cancer models in vitro and in vivo [abstract 1643]. Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2-6 April 2011; Orlando, FL. 2011, Philadelphia, PA: AACR
80.
Zurück zum Zitat Trudel S, Stewart AK, Rom E, Wei E, Li ZH, Kotzer S, Chumakov I, Singer Y, Chang H, Liang SB, Yayon A: The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells. Blood. 2006, 107: 4039-4046. 10.1182/blood-2005-10-4179.CrossRefPubMed Trudel S, Stewart AK, Rom E, Wei E, Li ZH, Kotzer S, Chumakov I, Singer Y, Chang H, Liang SB, Yayon A: The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells. Blood. 2006, 107: 4039-4046. 10.1182/blood-2005-10-4179.CrossRefPubMed
Metadaten
Titel
Challenges and opportunities in the targeting of fibroblast growth factor receptors in breast cancer
verfasst von
Vikram K Jain
Nicholas C Turner
Publikationsdatum
01.06.2012
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 3/2012
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3139

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