Drug Resistance Updates
Volume 12, Issue 4 , Pages 95-102 , August 2009

The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer

  • Scott A. Kono

      Affiliations

    • Department of Medicine, University of Colorado at Denver Anschutz Medical Campus, Aurora, CO 80045, United States
    • ,
  • Marianne E. Marshall

      Affiliations

    • Department of Craniofacial Biology, University of Colorado at Denver Anschutz Medical Campus, Aurora, CO 80045, United States
    • ,
  • Kathryn E. Ware

      Affiliations

    • Department of Craniofacial Biology, University of Colorado at Denver Anschutz Medical Campus, Aurora, CO 80045, United States
    • ,
  • Lynn E. Heasley

      Affiliations

    • Department of Craniofacial Biology, University of Colorado at Denver Anschutz Medical Campus, Aurora, CO 80045, United States
    • Corresponding Author InformationCorresponding author at: Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Denver Anschutz Medical Campus, Mail Stop 8120, P.O. Box 6511, Aurora, CO 80045, United States. Fax: +1 303 724 4580.

Received 15 April 2009 ,Revised 9 May 2009 ,Accepted 11 May 2009.

References 

  1. Ankrapp DP, Bevan DR. Insulin-like growth factor-I and human lung fibroblast-derived insulin-like growth factor-I stimulate the proliferation of human lung carcinoma cells in vitro. Cancer Res. 1993;53:3399–3404
  2. Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl. Acad. Sci. (USA). 2007;104:20932–20937
  3. Behrens C, Lin HY, Lee JJ, Raso MG, Hong WK, Wistuba II, et al. Immunohistochemical expression of basic fibroblast growth factor and fibroblast growth factor receptors 1 and 2 in the pathogenesis of lung cancer. Clin. Cancer Res. 2008;14:6014–6022
  4. Berger W, Setinek U, Mohr T, Kindas-Mugge I, Vetterlein M, Dekan G, et al. Evidence for a role of FGF-2 and FGF receptors in the proliferation of non-small cell lung cancer cells. Int. J. Cancer. 1999;83:415–423
  5. Bhide RS, Cai ZW, Zhang YZ, Qian L, Wei D, Barbosa S, et al. Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J. Med. Chem. 2006;49:2143–2146
  6. Brattstrom D, Bergqvist M, Hesselius P, Larsson A, Lamberg K, Wernlund J, et al. Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients. Lung Cancer. 2002;37:57–63
  7. Brattstrom D, Bergqvist M, Hesselius P, Larsson A, Wagenius G, Brodin O. Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer. Lung Cancer. 2004;43:55–62
  8. Camp ER, Summy J, Bauer TW, Liu W, Gallick GE, Ellis LM. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin. Cancer Res. 2005;11:397–405
  9. Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J. Natl. Cancer Inst. 2005;97:643–655
  10. Cappuzzo F, Toschi L, Tallini G, Ceresoli GL, Domenichini I, Bartolini S, et al. Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib. Ann. Oncol. 2006;17:1120–1127
  11. Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat. Rev. Cancer. 2004;4:118–132
  12. Chandler LA, Sosnowski BA, Greenlees L, Aukerman SL, Baird A, Pierce GF. Prevalent expression of fibroblast growth factor (FGF) receptors and FGF2 in human tumor cell lines. Int. J. Cancer. 1999;81:451–458
  13. Coldren CD, Helfrich BA, Witta SE, Sugita M, Lapadat R, Zeng C, et al. Baseline gene expression predicts sensitivity to gefitinib in non-small cell lung cancer cell lines. Mol. Cancer Res. 2006;4:521–528
  14. Cox AD, Der CJ. The dark side of Ras: regulation of apoptosis. Oncogene. 2003;22:8999–9006
  15. Croce CM. Oncogenes and cancer. N. Engl. J. Med. 2008;358:502–511
  16. Dancey JE. Predictive factors for epidermal growth factor receptor inhibitors--the bull's-eye hits the arrow. Cancer Cell. 2004;5:411–415
  17. Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455:1069–1075
  18. Dong AQ, Kong MJ, Ma ZY, Qian JF, Xu XH. Down-regulation of IGF-IR using small, interfering, hairpin RNA (siRNA) inhibits growth of human lung cancer cell line A549 in vitro and in nude mice. Cell Biol. Int. 2007;31:500–507
  19. Donnem T, Al-Shibli K, Al-Saad S, Busund LT, Bremnes RM. Prognostic impact of fibroblast growth factor 2 in non-small cell lung cancer: coexpression with VEGFR-3 and PDGF-B predicts poor survival. J. Thorac. Oncol. 2009;4:578–585
  20. Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc. Natl. Acad. Sci. (USA). 2008;105:8713–8717
  21. Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J. Clin. Oncol. 2005;23:5900–5909
  22. Engelman JA, Janne PA. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin. Cancer Res. 2008;14:2895–2899
  23. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–1043
  24. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139–149
  25. Fischer H, Taylor N, Allerstorfer S, Grusch M, Sonvilla G, Holzmann K, et al. Fibroblast growth factor receptor-mediated signals contribute to the malignant phenotype of non-small cell lung cancer cells: therapeutic implications and synergism with epidermal growth factor receptor inhibition. Mol. Cancer Ther. 2008;7:3408–3419
  26. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev. 2005;16:179–186
  27. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70
  28. Hennequin LF, Stokes ES, Thomas AP, Johnstone C, Ple PA, Ogilvie DJ, et al. Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J. Med. Chem. 2002;45:1300–1312
  29. Herbst RS, Heymach JV, Lippman SM. Lung cancer. New Engl. J. Med. 2008;359:1367–1380
  30. Hirsch FR, Varella-Garcia M, Bunn PA, Di Maria MV, Veve R, Bremmes RM, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J. Clin. Oncol. 2003;21:3798–3807
  31. Jang JH, Shin KH, Park JG. Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. Cancer Res. 2001;61:3541–3543
  32. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics. CA Cancer J. Clin. 2008;58:71–96
  33. Koziczak M, Holbro T, Hynes NE. Blocking of FGFR signaling inhibits breast cancer cell proliferation through downregulation of D-type cyclins. Oncogene. 2004;23:3501–3508
  34. Kuhn H, Kopff C, Konrad J, Riedel A, Gessner C, Wirtz H. Influence of basic fibroblast growth factor on the proliferation of non-small cell lung cancer cell lines. Lung Cancer. 2004;44:167–174
  35. Kumar R, Knick VB, Rudolph SK, Johnson JH, Crosby RM, Crouthamel MC, et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol. Cancer Ther. 2007;6:2012–2021
  36. Kwabi-Addo B, Ozen M, Ittmann M. The role of fibroblast growth factors and their receptors in prostate cancer. Endocr. Relat. Cancer. 2004;11:709–724
  37. Kwabi-Addo B, Ropiquet F, Giri D, Ittmann M. Alternative splicing of fibroblast growth factor receptors in human prostate cancer. Prostate. 2001;46:163–172
  38. Lee CT, Wu S, Gabrilovich D, Chen H, Nadaf-Rahrov S, Ciernik IF, et al. Antitumor effects of an adenovirus expressing antisense insulin-like growth factor I receptor on human lung cancer cell lines. Cancer Res. 1996;56:3038–3041
  39. Lee SH, Lopes de Menezes D, Vora J, Harris A, Ye H, Nordahl L, et al. In vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon cancer models. Clin. Cancer Res. 2005;11:3633–3641
  40. Lutterbach B, Zeng Q, Davis LJ, Hatch H, Hang G, Kohl NE, et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res. 2007;67:2081–2088
  41. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 2004;350:2129–2139
  42. Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, Fox EA, et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 2005;65:1479–1488
  43. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912–1934
  44. Marek L, Ware KE, Fritzsche A, Hercule P, Helton WR, Smith JE, 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
  45. Martinez-Torrecuadrada J, Cifuentes G, Lopez-Serra P, Saenz P, Martinez A, Casal JI. Targeting the extracellular domain of fibroblast growth factor receptor 3 with human single-chain Fv antibodies inhibits bladder carcinoma cell line proliferation. Clin. Cancer Res. 2005;11:6280–6290
  46. McDermott LA, Simcox M, Higgins B, Nevins T, Kolinsky K, Smith M, et al. RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and biological evaluation. Bioorg. Med. Chem. 2005;13:4835–4841
  47. McDermott U, Sharma SV, Dowell L, Greninger P, Montagut C, Lamb J, et al. Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc. Natl. Acad. USA. 2007;104:19936–19941
  48. McDermott U, Ames RY, Iafrate AJ, Maheswaran S, Stubbs H, Greninger P, et al. Ligand-dependent platelet-derived growth factor receptor (PDGFR)-α activation sensitizes rare lung cancer and sarcoma cells to PDGFR kinase inhibitors. Cancer Res. 2009;69:3937–3946
  49. Minuto F, Del Monte P, Barreca A, Fortini P, Cariola G, Catrambone G, et al. Evidence for an increased somatomedin-C/insulin-like growth factor I content in primary human lung tumors. Cancer Res. 1986;46:985–988
  50. Mitsudomi T, Yatabe Y. Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer. Cancer Sci. 2007;98:1817–1824
  51. Mohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, et al. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 1998;17:5896–5904
  52. Mohammadi M, Olsen SK, Ibrahimi OA. Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev. 2005;16:107–137
  53. Morgillo F, Kim WY, Kim ES, Ciardiello F, Hong WK, Lee HY. Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin. Cancer Res. 2007;13:2795–2803
  54. Morgillo F, Lee HY. Resistance to epidermal growth factor receptor-targeted therapy. Drug Resist. Updat. 2005;8:298–310
  55. Muller-Tidow C, Diederichs S, Bulk E, Pohle T, Steffen B, Schwable J, et al. Identification of metastasis-associated receptor tyrosine kinases in non-small cell lung cancer. Cancer Res. 2005;65:1778–1782
  56. Nguyen M, Watanabe H, Budson AE, Richie JP, Hayes DF, Folkman J. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J. Natl. Cancer Inst. 1994;86:356–361
  57. Nikolinakos P, Heymach JV. The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies. J. Thorac. Oncol. 2008;3:S131–134
  58. Ogawa T, Takayama K, Takakura N, Kitano S, Ueno H. Anti-tumor angiogenesis therapy using soluble receptors: enhanced inhibition of tumor growth when soluble fibroblast growth factor receptor-1 is used with soluble vascular endothelial growth factor receptor. Cancer Gene Ther. 2002;9:633–640
  59. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–1500
  60. Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2:e17
  61. Payson RA, Wu J, Liu Y, Chiu IM. The human FGF-8 gene localizes on chromosome 10q24 and is subjected to induction by androgen in breast cancer cells. Oncogene. 1996;13:47–53
  62. Platero S, Mokliatchouk O, Jayson GC, Jonker DJ, Rosen LS, Luroe S, et al. Correlation of FGF2 tumor expression with tumor response, PFS, and changes in plasma pharmacodynamic (PD) markers following treatment with brivanib alaninate, an oral dual inhibitor of VEGFR and FGFR tyrosine kinases. J. Clin. Oncol. 2008;26:3506
  63. Pollock PM, Gartside MG, Dejeza LC, Powell MA, Mallon MA, Davies H, et al. Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. Oncogene. 2007;26:7158–7162
  64. Quinn KA, Treston AM, Unsworth EJ, Miller MJ, Vos M, Grimley C, et al. Insulin-like growth factor expression in human cancer cell lines. J. Biol. Chem. 1996;271:11477–11483
  65. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131:1190–1203
  66. Sabbah M, Emami S, Redeuilh G, Julien S, Prévost G, Zimber A, et al. Molecular signature and therapeutic perspective of the epitelial-to-mesenchymal transitions in epithelial cancers. Drug Resist. Updat. 2008;11:123–151
  67. Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, 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;14:2075–2081
  68. Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J. Clin. Oncol. 2007;25:587–595
  69. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. New Engl. J. Med. 2005;353:123–132
  70. Shieh YS, Lai CY, Kao YR, Shiah SG, Chu YW, Lee HS, et al. Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia. 2005;7:1058–1064
  71. Siegfried JM, Weissfeld LA, Luketich JD, Weyant RJ, Gubish CT, Landreneau RJ. The clinical significance of hepatocyte growth factor for non-small cell lung cancer. Ann. Thorac Surg. 1998;66:1915–1918
  72. Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, et al. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science. 2007;318:287–290
  73. Sun HD, Malabunga M, Tonra JR, DiRenzo R, Carrick FE, Zheng H, 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:E964–976
  74. Sun L, Liang C, Shirazian S, Zhou Y, Miller T, Cui J, et al. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J. Med. Chem. 2003;46:1116–1119
  75. Suyama K, Shapiro I, Guttman M, Hazan RB. A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell. 2002;2:301–314
  76. Takeda M, Arao T, Yokote H, Komatsu T, Yanagihara K, Sasaki 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
  77. Thomson S, Petti F, Sujka-Kwok I, Epstein D, Haley JD. Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy. Clin. Exp. Metastasis. 2008;25:843–854
  78. Ueno K, Inoue Y, Kawaguchi T, Hosoe S, Kawahara M. Increased serum levels of basic fibroblast growth factor in lung cancer patients: relevance to response of therapy and prognosis. Lung Cancer. 2001;31:213–219
  79. van Leeuwen F, Nusse R. Oncogene activation and oncogene cooperation in MMTV-induced mouse mammary cancer. Semin. Cancer Biol. 1995;6:127–133
  80. Volm M, Koomagi R, Mattern J, Stammler G. Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas. Eur. J. Cancer. 1997;33:691–693
  81. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005;65:4389–4400
  82. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64:7099–7109
  83. Wimmel A, Glitz D, Kraus A, Roeder J, Schuermann M. Axl receptor tyrosine kinase expression in human lung cancer cell lines correlates with cellular adhesion. Eur. J. Cancer. 2001;37:2264–2274
  84. Xin X, Abrams TJ, Hollenbach PW, Rendahl KG, Tang Y, Oei YA, et al. CHIR-258 is efficacious in a newly developed fibroblast growth factor receptor 3-expressing orthotopic multiple myeloma model in mice. Clin. Cancer Res. 2006;12:4908–4915
  85. Yano S, Wang W, Li Q, Matsumoto K, Sakurama H, Nakamura T, et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res. 2008;68:9479–9487
  86. Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J. Biol. Chem. 2006;281:15694–15700

PII: S1368-7646(09)00028-4

doi: 10.1016/j.drup.2009.05.001

Drug Resistance Updates
Volume 12, Issue 4 , Pages 95-102 , August 2009

Article Tools

* Image Usage & Resolution