Clinical and Translational Oncology

, Volume 12, Issue 4, pp 253–260 | Cite as

C-MET as a new therapeutic target for the development of novel anticancer drugs

  • Israel Cañadas
  • Federico Rojo
  • Montserrat Arumí-Uría
  • Ana Rovira
  • Joan Albanell
  • Edurne ArriolaEmail author
Educational Series Molecular Targets in Oncology


MET is a tyrosine kinase receptor that, upon binding of its natural ligand, the hepatocyte growth factor (HGF), is phosphorylated and subsequently activates different signalling pathways involved in proliferation, motility, migration and invasion. MET has been found to be aberrantly activated in human cancer via mutation, amplification or protein overexpression. MET expression and activation have been associated with prognosis in a number of tumour types and predict response to MET inhibitors in preclinical models. Here we review the HGF/MET signalling pathway, its role in human cancer and the different inhibitory strategies that have been developed for therapeutic use.


MET HGF Small molecule inhibitors Antibodies 


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  1. 1.
    Benvenuti S, Comoglio PM (2007) The MET receptor tyrosine kinase in invasion and metastasis. J Cell Physiol 213:316–325PubMedCrossRefGoogle Scholar
  2. 2.
    Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF (2003) Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4:915–925PubMedCrossRefGoogle Scholar
  3. 3.
    Trusolino L, Comoglio PM (2002) Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer 2:289–300PubMedCrossRefGoogle Scholar
  4. 4.
    Peschard P, Fournier TM, Lamorte L et al (2001) Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein. Mol Cell 8:995–1004PubMedCrossRefGoogle Scholar
  5. 5.
    Abella JV, Peschard P, Naujokas MA et al (2005) Met/hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Mol Cell Biol 25:9632–9645PubMedCrossRefGoogle Scholar
  6. 6.
    Stoker M, Gherardi E, Perryman M, Gray J (1987) Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 327:239–242PubMedCrossRefGoogle Scholar
  7. 7.
    Gherardi E, Gray J, Stoker M et al (1989) Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc Natl Acad Sci U S A 86:5844–5848PubMedCrossRefGoogle Scholar
  8. 8.
    Nakamura T, Teramoto H, Ichihara A (1986) Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci U S A 83:6489–6493PubMedCrossRefGoogle Scholar
  9. 9.
    Naldini L, Weidner KM, Vigna E et al (1991) Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. Embo J 10:2867–2878PubMedGoogle Scholar
  10. 10.
    Comoglio PM, Giordano S, Trusolino L (2008) Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 7:504–516PubMedCrossRefGoogle Scholar
  11. 11.
    Stamos J, Lazarus RA, Yao X (2004) Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. Embo J 23: 2325–2335PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang YW, Vande Woude GF (2003) HGF/SF-met signaling in the control of branching morphogenesis and invasion. J Cell Biochem 88:408–417PubMedCrossRefGoogle Scholar
  13. 13.
    Corso S, Comoglio PM, Giordano S (2005) Cancer therapy: can the challenge be MET? Trends Mol Med 11:284–292PubMedCrossRefGoogle Scholar
  14. 14.
    Boccaccio C, Comoglio PM (2006) Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nat Rev Cancer 6:637–645PubMedCrossRefGoogle Scholar
  15. 15.
    Eder JP, Vande Woude GF, Boerner SA, LoRusso PM (2009) Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin Cancer Res 15:2207–2214PubMedCrossRefGoogle Scholar
  16. 16.
    Zeng Q, Chen S, You Z et al (2002) Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B. J Biol Chem 277:25203–25208PubMedCrossRefGoogle Scholar
  17. 17.
    Tulasne D, Foveau B (2008) The shadow of death on the MET tyrosine kinase receptor. Cell Death Differ 15:427–434PubMedCrossRefGoogle Scholar
  18. 18.
    Migliore C, Giordano S (2008) Molecular cancer therapy: can our expectation be MET? Eur J Cancer 44:641–651PubMedCrossRefGoogle Scholar
  19. 19.
    Birchmeier C, Gherardi E (1998) Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 8:404–410PubMedCrossRefGoogle Scholar
  20. 20.
    Schmidt L, Duh FM, Chen F et al (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16:68–73PubMedCrossRefGoogle Scholar
  21. 21.
    Maina F, Casagranda F, Audero E et al (1996) Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development. Cell 87:531–542PubMedCrossRefGoogle Scholar
  22. 22.
    Maina F, Pante G, Helmbacher F et al (2001) Coupling Met to specific pathways results in distinct developmental outcomes. Mol Cell 7:1293–1306PubMedCrossRefGoogle Scholar
  23. 23.
    Huh CG, Factor VM, Sanchez A (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A 101:4477–4482PubMedCrossRefGoogle Scholar
  24. 24.
    Iyer A, Kmiecik TE, Park M et al (1990) Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene. Cell Growth Differ 1:87–95PubMedGoogle Scholar
  25. 25.
    Christensen JG, Burrows J, Salgia R (2005) c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett 225:1–26PubMedCrossRefGoogle Scholar
  26. 26.
    Zhang YW, Su Y, Volpert OV, Vande Woude GF (2003) Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc Natl Acad Sci U S A 100:12718–12723PubMedCrossRefGoogle Scholar
  27. 27.
    Cooper CS, Park M, Blair DG et al (1984) Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311:29–33PubMedCrossRefGoogle Scholar
  28. 28.
    Liang TJ, Reid AE, Xavier R (1996) Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. J Clin Invest 97:2872–2877PubMedCrossRefGoogle Scholar
  29. 29.
    Soman NR, Correa P, Ruiz BA, Wogan GN (1991) The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc Natl Acad Sci U S A 88:4892–4896PubMedCrossRefGoogle Scholar
  30. 30.
    Smolen GA, Sordella R, Muir B et al (2006) Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc Natl Acad Sci U S A 103:2316–2321PubMedCrossRefGoogle Scholar
  31. 31.
    Engelman JA, Zejnullahu K, Mitsudomi T et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316:1039–1043PubMedCrossRefGoogle Scholar
  32. 32.
    Carracedo A, Egervari K, Salido M et al (2009) FISH and immunohistochemical status of the hepatocyte growth factor receptor (c-Met) in 184 invasive breast tumors. Breast Cancer Res 11:402PubMedCrossRefGoogle Scholar
  33. 33.
    Taulli R, Scuoppo C, Bersani F et al (2006) Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma. Cancer Res 66:4742–4749PubMedCrossRefGoogle Scholar
  34. 34.
    Houldsworth J, Cordon-Cardo C, Ladanyi M et al (1990) Gene amplification in gastric and esophageal adenocarcinomas. Cancer Res 50:6417–6422PubMedGoogle Scholar
  35. 35.
    Umeki K, Shiota G, Kawasaki H (1999) Clinical significance of c-met oncogene alterations in human colorectal cancer. Oncology 56:314–321PubMedCrossRefGoogle Scholar
  36. 36.
    Bean J, Brennan C, Shih JY et al (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A 104:20932–20937PubMedCrossRefGoogle Scholar
  37. 37.
    Tong CY, Hui AB, Yin XL (2004) Detection of oncogene amplifications in medulloblastomas by comparative genomic hybridization and arraybased comparative genomic hybridization. J Neurosurg 100:187–193PubMedGoogle Scholar
  38. 38.
    Beroukhim R, Getz G, Nghiemphu L et al (2007) Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci U S A 104:20007–20012PubMedCrossRefGoogle Scholar
  39. 39.
    Cappuzzo F, Marchetti A, Skokan M et al (2009) Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol 27:1667–1674PubMedCrossRefGoogle Scholar
  40. 40.
    Go H, Jeon YK, Park HJ et al (2010) High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer. J Thorac Oncol 5(3):305–313PubMedCrossRefGoogle Scholar
  41. 41.
    Zeng ZS, Weiser MR, Kuntz E et al (2008) c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases. Cancer Lett 265:258–269PubMedCrossRefGoogle Scholar
  42. 42.
    Park WS, Dong SM, Kim SY et al (1999) Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res 59:307–310PubMedGoogle Scholar
  43. 43.
    Lee JH, Han SU, Cho H et al (2000) A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19:4947–4953PubMedCrossRefGoogle Scholar
  44. 44.
    Seiwert TY, Jagadeeswaran R, Faoro L et al (2009) The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. Cancer Res 69:3021–3031PubMedCrossRefGoogle Scholar
  45. 45.
    Sattler M, Salgia R (2007) c-Met and hepatocyte growth factor: potential as novel targets in cancer therapy. Curr Oncol Rep 9:102–108PubMedCrossRefGoogle Scholar
  46. 46.
    Ma PC, Kijima T, Maulik G et al (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63:6272–6281PubMedGoogle Scholar
  47. 47.
    Ma PC, Jagadeeswaran R, Jagadeesh S et al (2005) 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 65:1479–1488PubMedCrossRefGoogle Scholar
  48. 48.
    Jagadeeswaran R, Ma PC, Seiwert TY et al (2006) Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma. Cancer Res 66:352–361PubMedCrossRefGoogle Scholar
  49. 49.
    Puri N, Ahmed S, Janamanchi V et al (2007) c-Met is a potentially new therapeutic target for treatment of human melanoma. Clin Cancer Res 13:2246–2253PubMedCrossRefGoogle Scholar
  50. 50.
    Puri N, Khramtsov A, Ahmed S et al (2007) A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angio genesis in mouse lung cancer xenografts. Cancer Res 67:3529–3534PubMedCrossRefGoogle Scholar
  51. 51.
    Jeffers M, Schmidt L, Nakaigawa N et al (1997) Activating mutations for the met tyrosine kinase receptor in human cancer. Proc Natl Acad Sci U S A 94:11445–11450PubMedCrossRefGoogle Scholar
  52. 52.
    Kong-Beltran M, Seshagiri S, Zha J et al (2006) Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res 66:283–289PubMedCrossRefGoogle Scholar
  53. 53.
    Graveel C, Su Y, Koeman J et al (2004) Activating Met mutations produce unique tumor profiles in mice with selective duplication of the mutant allele. Proc Natl Acad Sci U S A 101:17198–17203PubMedCrossRefGoogle Scholar
  54. 54.
    Di Renzo MF, Olivero M, Martone T et al (2000) Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 19:1547–1555PubMedCrossRefGoogle Scholar
  55. 55.
    Aebersold DM, Landt O, Berthou S et al (2003) Prevalence and clinical impact of Met Y1253Dactivating point mutation in radiotherapy-treated squamous cell cancer of the oropharynx. Oncogene 22:8519–8523PubMedCrossRefGoogle Scholar
  56. 56.
    Lorenzato A, Olivero M, Patane S et al (2002) Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion. Cancer Res 62:7025–7030PubMedGoogle Scholar
  57. 57.
    Cañadas I, Arumi M, Lema L et al (2009) MET in small cell lung carcinoma (SCLC): effects of a MET inhibitor in SCLC cell lines and prognostic role of MET status in patients. J Clin Oncol (ASCO Meeting Abstracts) 27:e14617Google Scholar
  58. 58.
    Danilkovitch-Miagkova A, Zbar B (2002) Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J Clin Invest 109:863–867PubMedGoogle Scholar
  59. 59.
    Ichimura E, Maeshima A, Nakajima T, Nakamura T (1996) Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res 87:1063–1069PubMedGoogle Scholar
  60. 60.
    Cipriani NA, Abidoye OO, Vokes E, Salgia R (2009) MET as a target for treatment of chest tumors. Lung Cancer 63:169–179PubMedCrossRefGoogle Scholar
  61. 61.
    Garcia S, Dales JP, Charafe-Jauffret E et al (2007) Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype. Hum Pathol 38:830–841PubMedCrossRefGoogle Scholar
  62. 62.
    Olivero M, Rizzo M, Madeddu R et al (1996) Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br J Cancer 74:1862–1868PubMedGoogle Scholar
  63. 63.
    Takanami I, Tanana F, Hashizume T et al (1996) Hepatocyte growth factor and c-Met/hepatocyte growth factor receptor in pulmonary adenocarcinomas: an evaluation of their expression as prognostic markers. Oncology 53:392–397PubMedCrossRefGoogle Scholar
  64. 64.
    Tsao MS, Liu N, Chen JR et al (1998) Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers. Lung Cancer 20:1–16PubMedCrossRefGoogle Scholar
  65. 65.
    Natali PG, Prat M, Nicotra MR et al (1996) Overexpression of the met/HGF receptor in renal cell carcinomas. Int J Cancer 69:212–217PubMedCrossRefGoogle Scholar
  66. 66.
    Di Renzo MF, Olivero M, Katsaros D et al (1994) Overexpression of the Met/HGF receptor in ovarian cancer. Int J Cancer 58:658–662PubMedCrossRefGoogle Scholar
  67. 67.
    Wong AS, Pelech SL, Woo MM et al (2001) Coexpression of hepatocyte growth factor-Met: an early step in ovarian carcinogenesis? Oncogene 20:1318–1328PubMedCrossRefGoogle Scholar
  68. 68.
    Garcia S, Dales JP, Jacquemier J et al (2007) c-Met overexpression in inflammatory breast carcinomas: automated quantification on tissue microarrays. Br J Cancer 96:329–335PubMedCrossRefGoogle Scholar
  69. 69.
    Takeuchi H, Bilchik A, Saha S et al (2003) c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases. Clin Cancer Res 9:1480–1488PubMedGoogle Scholar
  70. 70.
    Sawada K, Radjabi AR, Shinomiya N et al (2007) c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer Res 67:1670–1679PubMedCrossRefGoogle Scholar
  71. 71.
    Tolgay Ocal I, Dolled-Filhart M, D’Aquila TG et al (2003) Tissue microarray-based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors. Cancer 97:1841–1848PubMedCrossRefGoogle Scholar
  72. 72.
    Gentile A, Trusolino L, Comoglio PM (2008) The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev 27:85–94PubMedCrossRefGoogle Scholar
  73. 73.
    Boccaccio C, Gaudino G, Gambarotta G et al (1994) Hepatocyte growth factor (HGF) receptor expression is inducible and is part of the delayed-early response to HGF. J Biol Chem 269:12846–12851PubMedGoogle Scholar
  74. 74.
    Aguirre Ghiso JA, Alonso DF, Farias EF et al (1999) Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Eur J Biochem 263:295–304PubMedCrossRefGoogle Scholar
  75. 75.
    Michieli P, Basilico C, Pennacchietti S et al (1999) Mutant Met-mediated transformation is ligand-dependent and can be inhibited by HGF antagonists. Oncogene 18:5221–5231PubMedCrossRefGoogle Scholar
  76. 76.
    Koochekpour S, Jeffers M, Rulong S et al (1997) Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 57:5391–5398PubMedGoogle Scholar
  77. 77.
    Tuck AB, Park M, Sterns EE et al (1996) Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. Am J Pathol 148:225–232PubMedGoogle Scholar
  78. 78.
    Ferracini R, Olivero M, Di Renzo MF et al (1996) Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas. Oncogene 12:1697–1705PubMedGoogle Scholar
  79. 79.
    Ferracini R, Di Renzo MF, Scotlandi K et al (1995) The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 10:739–749PubMedGoogle Scholar
  80. 80.
    Rong S, Segal S, Anver M et al (1994) Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci U S A 91:4731–4735PubMedCrossRefGoogle Scholar
  81. 81.
    Lokker NA, Mark MR, Luis EA et al (1992) Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. Embo J 11:2503–2510PubMedGoogle Scholar
  82. 82.
    Lietha D, Chirgadze DY, Mulloy B et al (2001) Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor. Embo J 20:5543–5555PubMedCrossRefGoogle Scholar
  83. 83.
    Matsumoto K, Kataoka H, Date K, Nakamura T (1998) Cooperative interaction between alpha- and beta-chains of hepatocyte growth factor on c-Met receptor confers ligand-induced receptor tyrosine phosphorylation and multiple biological responses. J Biol Chem 273:22913–22920PubMedCrossRefGoogle Scholar
  84. 84.
    Trusolino L, Pugliese L, Comoglio PM (1998) Interactions between scatter factors and their receptors: hints for therapeutic applications. Faseb J 12:1267–1280PubMedGoogle Scholar
  85. 85.
    Chan AM, Rubin JS, Bottaro DP et al (1991) Identification of a competitive HGF antagonist encoded by an alternative transcript. Science 254: 1382–1385PubMedCrossRefGoogle Scholar
  86. 86.
    Montesano R, Soriano JV, Malinda KM (1998) Differential effects of hepatocyte growth factor isoforms on epithelial and endothelial tubulogenesis. Cell Growth Differ 9:355–365PubMedGoogle Scholar
  87. 87.
    Matsumoto K, Nakamura T (2003) NK4 (HGF-antagonist/angiogenesis inhibitor) in cancer biology and therapeutics. Cancer Sci 94:321–327PubMedCrossRefGoogle Scholar
  88. 88.
    Matsumoto K, Nakamura T (2008) NK4 gene therapy targeting HGF-Met and angiogenesis. Front Biosci 13:1943–1951PubMedCrossRefGoogle Scholar
  89. 89.
    Mazzone M, Basilico C, Cavassa S et al (2004) An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice. J Clin Invest 114:1418–1432PubMedGoogle Scholar
  90. 90.
    Michieli P, Mazzone M, Basilico C et al (2004) Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 6:61–73PubMedCrossRefGoogle Scholar
  91. 91.
    Kong-Beltran M, Stamos J, Wickramasinghe D (2004) The Sema domain of Met is necessary for receptor dimerization and activation. Cancer Cell 6:75–84PubMedCrossRefGoogle Scholar
  92. 92.
    Martens T, Schmidt NO, Eckerich C et al (2006) A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin Cancer Res 12:6144–6152PubMedCrossRefGoogle Scholar
  93. 93.
    Petrelli A, Circosta P, Granziero L et al (2006) Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity. Proc Natl Acad Sci U S A 103:5090–5095PubMedCrossRefGoogle Scholar
  94. 94.
    Kim KJ, Wang L, Su YC et al (2006) Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. Clin Cancer Res 12:1292–1298PubMedCrossRefGoogle Scholar
  95. 95.
    Jun HT, Sun J, Rex K (2007) AMG 102, a fully human anti-hepatocyte growth factor/scatter factor neutralizing antibody, enhances the efficacy of temozolomide or docetaxel in U-87 MG cells and xenografts. Clin Cancer Res 13:6735–6742PubMedCrossRefGoogle Scholar
  96. 96.
    Morotti A, Mila S, Accornero P, et al (2002) K252a inhibits the oncogenic properties of Met, the HGF receptor. Oncogene 21:4885–4893PubMedCrossRefGoogle Scholar
  97. 97.
    Sattler M, Pride YB, Ma P et al (2003) A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer Res 63:5462–5469PubMedGoogle Scholar
  98. 98.
    Christensen JG, Schreck R, Burrows J et al (2003) A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res 63:7345–7355PubMedGoogle Scholar
  99. 99.
    Berthou S, Aebersold DM, Schmidt LS et al (2004) The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants. Oncogene 23:5387–5393PubMedCrossRefGoogle Scholar
  100. 100.
    Zou HY, Li Q, Lee JH et al (2007) An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res 67:4408–4417PubMedCrossRefGoogle Scholar
  101. 101.
    Zhang Y, Guessous F, Kofman A et al (2010) XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC. IDrugs 13:112–121PubMedGoogle Scholar
  102. 102.
    Welsh JW, Mahadevan D, Ellsworth R et al (2009) The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells. Radiat Oncol 4:69PubMedCrossRefGoogle Scholar
  103. 103.
    Buchanan SG, Hendle J, Lee PS et al (2009) SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther 8:3181–3190PubMedCrossRefGoogle Scholar

Copyright information

© Feseo 2010

Authors and Affiliations

  • Israel Cañadas
    • 1
  • Federico Rojo
    • 1
    • 2
  • Montserrat Arumí-Uría
    • 1
    • 3
  • Ana Rovira
    • 1
  • Joan Albanell
    • 4
  • Edurne Arriola
    • 1
    • 4
    • 5
    Email author
  1. 1.Molecular Therapeutics and Biomarkers in Cancer LaboratoryInstitut Municipal d’Investigacions Mediques (IMIM) Hospital del MarBarcelonaSpain
  2. 2.Pathology DepartmentCapio-Fundación Jiménez DíazMadridSpain
  3. 3.Pathology DepartmentHospital del MarBarcelonaSpain
  4. 4.Oncology DepartmentHospital del MarBarcelonaSpain
  5. 5.Oncology DepartmentHospital del Mar — Parc de Salut MarBarcelonaSpain

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