MET as a potential target for the treatment of upper gastrointestinal cancers: Characterization of novel c-Met inhibitors from bench to bedside

Current Medicinal Chemistry

Volumn 21, Issue 8, 2014, Pages 975-989

  Avan, A ^a,b   Maftouh, M ^a   Funel, N ^c   Ghayour Mobarhan, M ^b   Boggi, U ^c   Peters, G J ^a   Giovannetti, E ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c UNIVERSITY OF PISA   (Italy)

Author keywords

Antitumor therapy; C Met inhibitors; Cancer aggressive behaviour; Clinical development; HGF; MET; Personalized medicine; Preclinical studies; Resistance to targeted agents; Upper gastrointestinal cancers

Indexed keywords

CABOZANTINIB; CRIZOTINIB; ENZYME ANTIBODY; FICLATUZUMAB; GOLVATINIB; JNJ 38877605; MESENCHYMAL EPITHELIAL TRANSITION FACTOR ANTIBODY; MGCD 265; MK 2461; PROTEIN TYROSINE KINASE INHIBITOR; RILOTUMUMAB; TAK 701; TIVANTINIB; UNCLASSIFIED DRUG;

ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER PROGNOSIS; CANCER RESISTANCE; CANCER STAGING; CANCER SURVIVAL; CELL PROLIFERATION; CONFORMATION; CRYSTAL STRUCTURE; DIGESTIVE SYSTEM CANCER; HINGE REGION; HUMAN; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; NONHUMAN; ONCOGENE RAS; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHENOTYPE; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SOLID TUMOR; STOMACH CANCER; TUMOR XENOGRAFT; UPREGULATION;

ANIMALS; ANTINEOPLASTIC AGENTS; GASTROINTESTINAL NEOPLASMS; GASTROINTESTINAL TRACT; HUMANS; MOLECULAR TARGETED THERAPY; PROTO-ONCOGENE PROTEINS C-MET; SIGNAL TRANSDUCTION;

EID: 84896325488     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113209990231     Document Type: Article

References (107)

1. Bottaro, D.P.; Rubin, J.S.; Faletto, D.L.; Chan, A.M.; Kmiecik, T.E.; Vande Woude, G.F.; Aaronson, S.A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science, 1991, 251, 802-804.
2. Cooper, C.S.; Park, M.; Blair, D.G. Tainsky, M.A. ; Huebner, K. ; Croce, C.M. ; Vande Woude, G.F. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature, 1984, 311, 29-33.
3. Liu, X.; Newton, R.C.; Scherle, P.A. Developing c-MET pathway inhibitors for cancer therapy: progress and challenges. Trends Mol. Med., 2010, 16, 37-45.
4. Gherardi, E.; Birchmeier, W.; Birchmeier, C.; Vande Woude, G. Targeting MET in cancer: rationale and progress. Nat. Rev. Cancer, 2012, 12, 89-103.
5. Bladt, F.; Riethmacher, D.; Isenmann, S.; Aguzzi, A.; Birchmeier, C. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature, 1995, 376, 768-771.
6. Streit, A.; Stern, C.D.; Thery, C, Ireland, G.W.; Aparicio, S.; Sharpe, M.J.; Gherardi, E. A role for HGF/SF in neural induction and its expression in Hensen's node during gastrulation. Development, 1995, 121, 813-824.
7. Andermarcher, E.; Surani, M.A.; Gherardi, E. Co-expression of the HGF/SF and c-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev. Genet., 1996, 18, 254-266.
8. Boccaccio, C.; Comoglio, P.M. Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nat. Rev. Cancer, 2006, 6, 637-645.
9. Liu, X.; Yao, W.; Newton, R.C.; Scherle, P.A. Targeting the c- MET signaling pathway for cancer therapy. Expert. Opin. Investig. Drugs, 2008, 17, 997-1011.
10. Sierra, J.R.; Tsao, M.S. c-MET as a potential therapeutic target and biomarker in cancer. Ther. Adv. Med. Oncol., 2011, 3, S21-S35.
11. Ponzetto, C.; Bardelli, A.; Zhen, Z.; Maina, F.; dalla Zonca, P.; Giordano, S.; Graziani, A.; Panayotou, G.; Comoglio, P.M. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell, 1994, 77, 261-271.
12. Furge, K.A.; Zhang, Y.W.; Vande-Woude, G.F. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene, 2000, 19, 5582-5589.
13. Johnson, G.L.; Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 2002, 298, 1911-1912.
14. Fan, S.; Gao, M.; Meng, Q.; Laterra, J.J.; Symons, M.H.; Coniglio, S.; Pestell, R.G.; Goldberg, I.D.; Rosen, E.M. Role of NF-kappaB signaling in hepatocyte growth factor/scatter factor-mediated cell protection. Oncogene, 2005, 24, 1749-1766.
15. Muller, M.; Morotti, A.; Ponzetto, C. Activation of NF-kappaB is essential for hepatocyte growth factor-mediated proliferation and tubulogenesis. Mol. Cell. Biol., 2002, 22, 1060-1072.
16. Siegfried, J.M.; Weissfeld, L.A.; Singh-Kaw, P.; Weyant, R.J.; Testa, J.R.; Landreneau, R.J. Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. Cancer Res., 1997, 57, 433-439.
17. Tsugawa, K.; Yonemura, Y.; Hirono, Y.; Fushida, S.; Kaji, M.; Miwa, K; Miyazaki, I.; Yamamoto, H. Amplification of the c- met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features. Oncology, 1998, 55, 475-481.
18. Birchmeier, C.; Birchmeier, W.; Gherardi, E.; Vande-Woude, G.F. Met, metastasis, motility and more. Nat. Rev. Mol. Cell. Biol., 2003, 4, 915-925.
19. Nakamura, Y.; Niki, T.; Goto, A.; Morikawa, T.; Miyazawa, K.; Nakajima, J.; Fukayama, M. c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer. Sci., 2007, 98, 1006-1013.
20. Conrotto, P.; Corso, S.; Gamberini, S.; Comoglio, P.M.; Giordano, S. Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene, 2004, 23, 5131-5137.
21. Capparuccia, L.; Tamagnone, L. Semaphorin signaling in cancer cells and in cells of the tumor microenvironment - two sides of a coin. J. Cell. Sci., 2009, 122, 1723-1736.
22. Lennerz, J.K.; Kwak, E.L.; Ackerman, A.; Michael, M.; Fox, S.B.; Bergethon, K.; Lauwers, G.Y.; Christensen, J.G.; Wilner, K.D.; Haber, D.A.; Salgia, R.; Bang, Y.J.; Clark, J.W.; Solomon, B.J.; Iafrate, A.J. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J. Clin. Oncol., 2011, 29, 4803-4810.
23. Christensen, J.G.; Burrows, J.; Salgia, R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer. Lett., 2005, 8, 1-26.
24. Lee, H.E.; Kim, M.A.; Lee, H, S.; Jung, E.J.; Yang, H.K,.; Lee, B.L.; Bang, Y, J.; Kim, W, H. MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome. Br. J. Cancer, 2012, 107, 325-333.
25. Rosen, P; Sweeney, C.; Rasmussen, E.; Shubhakar, P.; Scripture, C.; Leitch I.; Lu, J.; Beaupre, D.M.; Yee. L.K. AMG 102, an HGF/SF antagonist, in combination with anti-angiogenesis targeted therapies in adult patients with advanced solid tumors. Proceedings of the American Society of Clinical Oncology meeting, San Diego, CA, April 12-16, 2008; J. Clin. Oncol., 2008, 26, 3570.
26. Avan, A.; Quint, K.; Nicolini, F.; Funel, N.; Frampton, A.E.; Maftouh, M.; Pelliccioni, S.; Schuurhuis, G.J.; Peters, G.J,.; Giovannetti, E. Enhancement Of The Antiproliferative Activity Of Gemcitabine By Modulation Of C-Met Pathway In Pancreatic Cancer. Curr. Pharm. Des., 2013, 19, 940-950.
27. Wang, X.L.; Chen, X.M.; Fang, J.P.; Yang, C.Q. Lentivirusmediated RNA silencing of c-Met markedly suppresses peritoneal dissemination of gastric cancer in vitro and in vivo. Acta. Pharmacol. Sin., 2012, 33, 513-522.
28. Schmidt, L.; Duh, F.M.; Chen, F.; Kishida, T.; Glenn, G.; Choyke, P.; Scherer, S.W.; Zhuang, Z.; Lubensky, I.; Dean, M.; Allikmets, R.; Chidambaram, A.; Bergerheim, U.R.; Feltis, J.T.; Casadevall, C.; Zamarron, A.; Bernues, M.; Richard, S.; Lips, C.J.; Walther, M.M.; Tsui, L.C.; Geil, L.; Orcutt, M.L.; Stackhouse, T.; Lipan, J.; Slife, L.; Brauch, H.; Decker, J.; Niehans, G.; Hughson, M.D.; Moch, H.; Storkel, S.; Lerman, M.I.; Linehan, W.M.; Zbar, B. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat. Genet., 1997, 16, 68-73.
29. Lee, J.H.; Han, S.U.; Cho, H.; Jennings, B.; Gerrard, B.; Dean, M.; Schmidt, L.; Zbar, B.; Vande-Woude, G.F. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene, 2000, 19, 4947-4953.
30. Zeng, Z.S.; Weiser, M.R.; Kuntz, E.; Chen, C.T.; Khan, S.A.; Forslund, A.; Nash, G.M.; Gimbel, M.; Yamaguchi, Y.; Culliford, A.T.; D'Alessio, M.; Barany, F.; Paty, P.B. c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases. Cancer Lett., 2008, 265, 258-269.
31. Graveel, C.; Su, Y.; Koeman, J.; Wang, L.M.; Tessarollo, L.; Fiscella, M.; Birchmeier, C.; Swiatek, P.; Bronson, R.; Vande-Woude, G. Activating Met mutations produce unique tumor profiles in mice with selective duplication of the mutant allele. Proc. Natl. Acad. Sci. USA., 2004, 101, 17198-17203.
32. Ma, P.C.; Tretiakova, M.S.; MacKinnon, A.C.; Ramnath, N.; Johnson, C.; Dietrich, S.; Seiwert, T.; Christensen, J.G.; Jagadeeswaran, R.; Krausz, T.; Vokes, E.E.; Husain, A.N.; Salgia, R. Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer, 2008, 47, 1025-1037.
33. Galvani, E.; Alfieri, R.; Giovannetti, E.; Cavazzoni, A; La Monica, S; Galetti, M; Fumarola, C; Bonelli, M.; Mor, M.; Tiseo, M; Peters, G.J.; Petronini, P.G., Ardizzoni, A. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Current Status and Future Perspectives in the Development of Novel Irreversible Inhibitors for the Treatment of Mutant Non-small Cell Lung Cancer. Curr. Pharm. Des., 2013, 19, 818-832.
34. Summy, J.M.; Gallick, G.E. Treatment for advanced tumors: SRC reclaims center stage. Clin. Cancer Res., 2006, 12, 1398-1401.
35. Alvarez, R.H.; Kantarjian, H.M.; Cortes, J.E. The role of Src in solid and hematologic malignancies: development of newgeneration Src inhibitors. Cancer, 2006, 107, 1918-1929.
36. Ivan, M.; Bond, J.A.; Prat, M.; Comoglio, P.M.; Winford-Thomas, D. Activated ras and ret oncogenes induce over-expression of c-met (hepatocyte growth factor receptor) in human thyroid epithelial cells. Oncogene, 1997, 14, 2417-2423.
37. Pennacchietti, S.; Michieli, P.; Galluzzo, M.; Mazzone, M.; Giordano, S.; Comoglio, P.M. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell., 2003, 3, 347-361.
38. Bhowmick, N.A.; Neilson, E.G.; Moses, H.L. Stromal fibroblasts in cancer initiation and progression. Nature, 2004, 432, 332-337.
39. Comoglio, P.M.; Giordano, S.; Trusolino, L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat. Rev. Drug. Discov., 2008, 7, 504-516.
40. Appleman, L.J. MET signaling pathway: a rational target for cancer therapy. J. Clin. Oncol., 2011, 29, 4837-4838.
41. Osada, S.; Kanematsu, M.; Imai, H.; Goshima, S. Clinical significance of serum HGF and c-Met expression in tumor tissue for evaluation of properties and treatment of hepatocellular carcinoma. Hepatogastroenterology, 2008, 55, 544-549.
42. Huang, T.J.; Wang, J.Y.; Lin, S.R.; Lian, S.T.; Hsieh, J.S. Overexpression of the c-met protooncogene in human gastric carcinoma - correlation to clinical features. Acta. Oncol., 2001, 40, 638-643.
43. Ke, A.W.; Shi, G.M.; Zhou, J.; Wu, F.Z.; Ding, Z.B.; Hu, M.Y.; Xu, Y.; Song, Z.J.; Wang, Z.J.; Wu, J.C.; Bai, D.S.; Li, J.C.; Liu, K.D.; Fan, J. Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma. Hepatology, 2009, 49, 491-503.
44. Li, C.; Wu, J.J.; Hynes, M.; Dosch, J.; Sarkar, B.; Welling, T.H.; Magliano, M.; Simeone, D.M. c-Met is a marker of pancreatic cancer stem cells and therapeutic target. Gastroenterology, 2011, 141, 2218-2227.
45. Zhu, G.H.; Huang, C.; Qiu, Z.J.; Liu, J.; Zhang, Z.H.; Zhao, N.; Feng, Z.Z.; Lv, X.H. Expression and prognostic significance of CD151, c-Met, and integrin alpha3/alpha6 in pancreatic ductal adenocarcinoma. Dig. Dis. Sci., 2011, 56, 1090-1098.
46. Graziano, F.; Galluccio, N.; Lorenzini, P.; Ruzzo, A.; Canestrari, E.; D'Emidio, S.; Catalano, V.; Sisti, V.; Ligorio, C.; Andreoni, F.; Rulli, E.; Di-Oto, E.; Fiorentini, G.; Zingaretti, C.; De Nictolis, M.; Cappuzzo, F.; Magnani, M. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J. Clin. Oncol., 2011, 29, 4789-4795.
47. Avan, A.; Caretti, V.; Funel, N.; Galvani, E.; Maftouh, M.; Honeywell, R.J.; Lagerweij, T.; Van Tellingen, O.; Campani, D.; Fuchs, D.; Verheul, H.M.; Schuurhuis, G.J.; Boggi, U.; Peters. G.J.; Würdinger, T.; Giovannetti, E. Crizotinib Inhibits Metabolic Inactivation of Gemcitabine in c-Met-driven Pancreatic Carcinoma. Cancer Res., 2013, 73, 6745-6756.
48. Smolen, G.A.; Sordella, R.; Muir, B.; Mohapatra, G.; Barmettler, A.; Archibald, H.; Kim, W.J.; Okimoto, R.A.; Bell, D.W.; Sgroi, D.C.; Christensen, J.G.; Settleman, J.; Haber, D.A. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc. Natl. Acad. Sci. USA, 2006, 103, 2316-2321.
49. Okamoto, W.; Okamoto, I.; Tanaka, K.; Hatashita, E.; Yamada, Y.; Kuwata, K.; Yamaguchi, H.; Arao, T.; Nishio, K.; Fukuoka, M.; Jänne, PA.; Nakagawa, K. TAK-701, a humanized monoclonal antibody to hepatocyte growth factor, reverses gefitinib resistance induced by tumor-derived HGF in non-small cell lung cancer with an EGFR mutation. Mol. Cancer. Ther., 2010, 9, 2785-2792.
50. Catenacci, D.V.; Henderson, L.; Xiao, S.Y.; Patel, P.; Yauch, R.L.; Hegde, P.; Zha, J.; Pandita, A.; Peterson, A.; Salgia, R. Durable complete response of metastatic gastric cancer with anti-Met therapy followed by resistance at recurrence. Cancer. Discov., 2011, 1, 573-579.
51. Yonemura, Y.; Kaji, M.; Hirono, Y.; Fushida, S.; Tsugawa, K.; Fujimura, T.; Miyazaki, I.; Harada, S.; Yamamoto, H. Correlation between overexpression of c-met gene and the progression of gastric cancer. Int. J. Oncol., 1996, 8, 555-560.
52. Amemiya, H.; Kono, K.; Itakura, J.; Tang, R.F.; Takahashi, A.; An, F.Q.; Kamei, S.; Iizuka, H.; Fujii, H.; Matsumoto, Y. c-Met expression in gastric cancer with liver metastasis. Oncology, 2002, 63, 286-296.
53. Toiyama, Y.; Yasuda, H.; Saigusa, S.; Matushita, K.; Fujikawa, H.; Tanaka, K.; Mohri, Y.; Inoue, Y.; Goel, A.; Kusunoki, M. Coexpression of hepatocyte growth factor and c-Met predicts peritoneal dissemination established by autocrine hepatocyte growth factor/ c-Met signaling in gastric cancer. Int. J. Cancer, 2012, 130, 2912-2921.
54. Di Renzo, M.F.; Poulsom, R.; Olivero, M.; Comoglio, P.M.; Lemoine, N.R. Expression of the Met/hepatocyte growth factor receptor in human pancreatic cancer. Cancer Res., 1995, 55, 1129-1138.
55. Ebert, M.; Yokoyama, M.; Friess, H.; Büchler, M.W.; Korc, M. Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer. Cancer Res., 1994, 54, 5775-5778.
56. Furukawa, T.; Duguid, W.P.; Kobari, M.; Matsuno, S.; Tsao, M.S. Hepatocyte growth factor and Met receptor expression in human pancreatic carcinogenesis. Am. J. Pathol., 1995, 147, 889-895.
57. Liu, N.; Furukawa, T.; Kobari, M.; Tsao, M.S. Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma. Am. J. Pathol., 1988, 153, 263-269.
58. Oshima, Y.; Suzuki, A.; Kawashimo, K.; Ishikawa, M.; Ohkohchi, N.; Taniguchi, H. Isolation of mouse pancreatic ductal progenitor cells expressing CD133 and c-Met by flow cytometric cell sorting. Gastroenterology, 2007, 132, 720-732.
59. Rovira, M.; Scott, S.G.; Liss, A.S.; Jensen, J.; Thayer, S.P.; Leach, S.D. Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc. Natl. Acad. Sci. USA, 2009, 107, 75-80.
60. Suzuki, A.; Nakauchi, H.; Taniguchi, H. Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes, 2004, 53, 2143-2152.
61. Jin, H.; Yang, R.; Zheng, Z.; Romero, M.; Ross, J.; Bou-Reslan, H.; Carano, R.A.; Kasman, I.; Mai, E.; Young, J.; Zha, J.; Zhang, Z.; Ross, S.; Schwall, R.; Colbern, G.; Merchant, M. MetMAB, the one-armed 5D5 anti-c-Met Antibody MetMAB, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Res., 2008, 68, 4360-4368.
62. Mascarenhas, J.B.; Young, K.P.; Littlejohn, E.L.; Yoo, B.K.; Salgia, R.; Lang, D. PAX6 is expressed in pancreatic cancer and actively participates in cancer progression through activation of the MET tyrosine kinase receptor gene. J. Biol. Chem., 2009, 284, 27524-27532.
63. Neesse. A.; Michl, P.; Frese, K.K.; Feig, C.; Cook, N.; Jacobetz, M.A.; Lolkema, M.P.; Buchholz, M.; Olive, K.P.; Gress, T.M.; Tuveson, D.A. Stromal biology and therapy in pancreatic cancer. Gut, 2011, 60, 861-868.
64. Shah, A.N.; Summy, J.M.; Zhang, J.; Park, S.I.; Parikh, N.U.; Gallick, G.E. Development and characterization of gemcitabineresistant pancreatic tumor cells. Ann. Surg. Oncol., 2007, 14, 3629-3637.
65. Logan-Collins, J.; Thomas, R.M.; Yu, P.; Jaquish, D.; Mose, E.; French, R.; Stuart, W.; McClaine, R.; Aronow, B.; Hoffman, R.M.; Waltz, S.E.; Lowy, A.M. Silencing of RON receptor signaling promotes apoptosis and gemcitabine sensitivity in pancreatic cancers. Cancer. Res., 2010, 70, 1130-1140.
66. De Bacco, F.; Luraghi, P.; Medico, E.; Reato, G.; Girolami, F.; Perera, T.; Gabriele, P.; Comoglio, P.M.; Boccaccio, C. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J. Natl. Cancer. Inst., 2011, 103, 645-661.
67. Chen, C.T.; Kim, H.; Liska, D.; Gao, S.; Christensen, J.G.; Weiser, M.R. MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol. Cancer Ther., 2012, 11, 660-669.
68. Dussault, I.; Bellon, S.F. From concept to reality: the long road to c-Met and RON receptor tyrosine kinase inhibitors for the treatment of cancer. Anticancer Agents Med. Chem., 2009, 9, 221-229.
69. Eathiraj, S.; Palma, R.; Volckova, E.; Hirschi, M.; France, D.S.; Ashwell, M.A.; Chan, T.C.K. Discovery of a Novel Mode of Protein Kinase Inhibition Characterized by the Mechanism of Inhibition of Human Mesenchymal-epithelial Transition Factor (c-Met) Protein Autophosphorylation by ARQ 197. J. Biol. Chem., 2011, 286, 20666-20676.
70. Gordon, M.S.; Sweeney, C.S.; Mendelson, D.S.; Eckhardt, S.G.; Anderson, A.; Beaupre, D.M.; Branstetter, D.; Burgess, T.L.; Coxon, A.; Deng, H.; Kaplan-Lefko, P.; Leitch, I.M.; Oliner, K.S.; Yan, L.; Zhu, M.; Gore, L.; Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factorneutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors. Clin. Cancer Res., 2010, 16, 699-710.
71. Patnaik, G.J.; Weiss, K.; Papadopoulos, R.; Tibes, A.W.; Tolcher, F.C.; Payumo, M.M.; Cotreau, J.; Jac, R.; Isaacs, R.K.; Ramanathan. Phase I study of SCH 900105 (SC), an anti-hepatocyte growth factor (HGF) monoclonal antibody (MAb), as a single agent and in combination with erlotinib (E) in patients (pts) with advanced solid tumors. J. Clin. Oncol., 2010, 28, 2525.
72. Moss, R.A.; Patel, P.; Bothos, J.; Peterson, A.C.; Eppler, S.; Yu, W.; Ratain, M.J.; Harris, K.; Mehnert, J.; Salgia, R. Complete results from phase I dose escalation study of MetMab, a monovalent antagonist antibody to the receptor MET, doses as single agent and in combination with bevacizumab in patients with advanced solid malignancies. Ann. Oncol., 2010, 21, 504.
73. Spigel, D.R.; Ervin, T.J.; Ramlau, R,; Daniel, D.B.; Goldschmidt, J.H.; Blumenschein, G.R.; Krzakowski, M.J. Final efficacy results from OAM4558g, a randomized phase II study evaluating Met- MAb or placebo in combination with erlotinib in advanced NSCLC. J. Clin. Oncol., 2011, 29, 7505.
74. Goldman, J.W.; Laux, I.; Chai, F.; Savage, R.E.; Ferrari, D.; Garmey, E.G.; Just, R.G.; Rosen, L.S. Phase 1 dose-escalation trial evaluating the combination of the selective MET inhibitor tivantinib (ARQ 197) plus erlotinib. Cancer, 2012, 118, 5903-5911.
75. Rosen, L.S.; Senzer, N.; Mekhail, T.; Ganapathi, R.; Chai, F.; Savage, R.E.; Waghorne, C.; Abbadessa, G.; Schwartz, B.; Dreicer, R. A phase I dose-escalation study of tivantinib (ARQ 197) in adult patients with metastatic solid tumors. Clin. Cancer. Res., 2011, 17, 7754-7764.
76. Adjei, A.A.; Schwartz, B.; Garmey, E. Early clinical development of ARQ 197, a selective, non-ATP-competitive inhibitor targeting MET tyrosine kinase for the treatment of advanced cancers. Oncologist, 2011, 16, 788-799.
77. Scagliotti, G.V.; Novello, S.; Schiller, J.H.; Hirsh, V.; Sequist, L.V.; Soria, J.C.; von Pawel, J.; Schwartz, B.; Von Roemeling, R.; Sandler, A, B. Rationale and Design of MARQUEE: A Phase III, Randomized, Double-Blind Study of Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Patients With Locally Advanced or Metastatic, Non-squamous, Non-Small-Cell Lung Cancer. Clin. Lung Cancer, 2012, 13, 391-395.
78. Nishina, T.; Hirashima, T.; Sugio, K. The effect of CYP2C19 polymorphism on the tolerability of ARQ 197: results from phase I trial in Japanese patients with metastatic solid tumors. J. Clin. Oncol., 2011, 29, 2516.
79. Camacho, L.H.; Bendell, J.C.; John-Reid, L.; Campos, L.T.; Jones, S.F; Kazakin, J.; Savage, R.; Schwartz, B.E.; Abbadessa, G.; Saleh M.N. Phase Ib dose-escalation trial evaluating c-MET inhibitor ARQ 197 administered in combination with gemcitabine to patients (pts) with advanced solid tumors. J. Clin. Oncol., 2010, 28, ASCO Annual Meeting Proceedings (Post-Meeting Edition).
80. Gandhi, L.; Jänne, P.A. Crizotinib for ALK-rearranged non-small cell lung cancer: a new targeted therapy for a new target. Clin. Cancer Res., 2012, 18, 3737-3742.
81. Iwahara, T.; Fujimoto, J.; Wen, D.; Cupples, R.; Bucay, N.; Arakawa, T.; Mori, S.; Ratzkin, B.; Yamamoto, T. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene, 1997, 14, 439-449.
82. Bazigou, E.; Apitz, H.; Johansson, J.; Lorén, C.E.; Hirst, E.M.; Chen, P.L.; Palmer, R.H.; Salecker, I. Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila. Cell, 2007, 128, 961-975.
83. Lipson, D.; Capelletti, M.; Yelensky, R.; Otto, G.; Parker, A.; Jarosz, M.; Curran, J.A.; Balasubramanian, S.; Bloom, T.; Brennan, K.W.; Donahue, A.; Downing, S.R.; Frampton, G.M.; Garcia, L.; Juhn, F.; Mitchell, K.C.; Stephens, P.J. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat. Med., 2012, 18, 382-384.
84. Kentsis, A.; Reed, C.; Rice, K.L.; Sanda, T.; Rodig, S.J.; Tholouli, E.; Christie, A.; Valk, P.J.; Delwel, R.; Kung, A.L.; Staudt, L.M. Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia. Nat. Med., 2012, 18, 1118-1122.
85. Ou, S.H.; Kwak, E.L.; Siwak-Tapp, C.; Dy J.; Bergethon, K.; Clark, J.W.; Camidge, D.R.; Solomon, B.J.; Maki, R.G.; Bang, Y.J.; Kim, D.W.; Christensen. J.; Tan, W.; Wilner, K.D.; Salgia, R.; Iafrate, A.J. Activity of crizotinib (PF02341066), a dual mesenchymal- epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J. Thorac. Oncol., 2011, 6, 942-946.
86. Komiya, T.; Thomas, A.; Khozin, S.; Rajan, A.; Wang, Y.; Giaccone, G. Response to crizotinib in ROS1-rearranged non-small-cell lung cancer. J. Clin. Oncol., 2012, 30, 3425-3426.
87. Sennino, B.; Ishiguro-Oonuma, T.; Wei, Y.; Naylor, R.M.; Williamson, C.W.; Bhagwandin, V.; Tabruyn, S.P.; You, W.K.; Chapman, H.A.; Christensen, J.G.; Aftab, D.T.; McDonald, D.M. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer Discov., 2012, 2, 270-287.
88. Gordon, M.S.; Vogelzang, N.J.; Schoffski, P. Activity of cabozantinib (XL184) in soft tissue and bone: results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors. J. Clin. Oncol., 2011, 29, 3010.
89. Hong, D.; LoRusso, P.; Kurzrock, R.; Maroun, C.; Mehran, M.; Drouin, M.; Martell, R.; Wheler, J. Phase I study of MGCD265 administered intermittently to patients with advanced malignancies (Study 265-102). J. Clin. Oncol., 2009, 27, e14516.
90. Heath E.I.; LoRusso, P.; Kurzrock, R.; Falchook, G.S.; Maroun, C.R.; Drouin, M.A.; Juretic, M.; Martell, R.E.; Besterman, J.M.; Wheler., J.J. A phase I study of oral administration of MGCD265 in patients with advanced malignancies (study 265-102). J. Clin. Oncol., 2010, 28, 15, 3108.
91. Beeram, M.; Patnaik, A.; Amaravadi, R.K.; Haas, N.B.; Papadopoulos, K.P.; O'Dwyer, P.J. MGCD265, a multitargeted oral tyrosine kinase receptor inhibitor of Met and VEGFR, in combination with docetaxel. J. Clin. Oncol., 2012, 30, e13604.
92. Perera, T.; Lavrijssen, T.; Janssens, B. JNJ-38877605: a selective Met kinase inhibitor inducing regression of Met-driven tumor models. Presented at the 99th AACR Annual Meeting; Apr 12-16, 2008; San Diego (CA): Abstr 4837.
93. Nakagawa, T.; Tohyama, O.; Yamaguchi, A.; Matsushima, T.; Takahashi, K.; Funasaka, S.; Shirotori, S.; Asada, M.; Obaishi, H. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci., 2010, 101, 210-215.
94. Pan, B.S.; Chan, G.K.; Chenard, M.; Chi, A.; Davis, L.J.; Deshmukh, S.V.; Kohl, N.E.; Dinsmore, C.J. MK-2461, novel multitargeted kinase inhibitor, preferentially inhibits the activated c- Met receptor. Cancer. Res., 2010, 70, 1524-1533.
95. Tanizaki J, Okamoto I, Okamoto K, Takezawa, K.; Kuwata, K.; Yamaguchi, H.; Nakagawa, K. MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in nonsmall cell lung cancer according to MET alterations. J. Thorac. Oncol., 2011, 6, 1624-1631.
96. Bang, Y.J.; Kwak E.L.; Shaw, A.T.; Camidge, D.R.; Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive patients with non-small cell lung cancer (NSCLC). J. Clin. Oncol., 2010, 28, 3.
97. Qi, J. ; McTigue, M.A.; Rogers, A.; Lifshits, E.; Christensen, J.G.; Jänne, P.A.; Engelman, J.A. Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors. Cancer Res., 2011, 71, 1081-1091.
98. Cepero, V.; Sierra, J.R.; Corso, S.; Ghiso, E.; Casorzo, L.; Perera, T.; Comoglio, P.M.; Giordano, S. MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors. Cancer Res., 2010, 70, 7580-7590.
99. Huang, S.; Hölzel, M.; Knijnenburg, T.; Schlicker, A.; Roepman, P.; McDermott, U.; Garnett, M.; Wessels, L.F.; Bernards, R. MED12 controls the response to multiple cancer drugs through regulation of TGF receptor signalling. Cell, 2012, 151, 937-950.
100. Feng, Y.; Thiagarajan, P.S.; Ma, P.C.; MET signaling: novel targeted inhibition and its clinical development in lung cancer. J. Thoracic. Oncol., 2012, 7, 459-467.
101. Bean, J.; Brennan, C.; Shih, J.Y.; Riely, G.; Viale, A.; Wang, L.; Chitale, D.; Motoi, N.; Szoke, J.; Broderick, S.; Balak, M.; Chang, W.C.; Yang, C.H.; Pao, W.; 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.
102. Wang, W.; Li, Q.; Takeuchi, S.; Nakagawa, T.; Uenaka., T.; Yano, S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin. Cancer. Res., 2012, 15, 1663-1671.
103. Zucali, P.A.; Ruiz, M.G.; Giovannetti, E.; Destro, A.; Roncalli, M.; Santoro, A.; Giaccone, G. Role of cMET expression in non-smallcell lung cancer patients treated with EGFR tyrosine kinase inhibitors. Ann. Oncol., 2008, 19, 1605-1612.
104. Organ, S.L.; Tsao, M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol., 2011, 3, S7-S19.
105. Xu, L.; Kikuchi, E.; Xu, C.; Ebi, H.; Ercan, D.; Cheng, K.A,; Padera, R.; Engelman, J.A.;, Jänne, P.A, Shapiro GI, Shimamura T, Wong KK. Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutantEGFR containing T790M and MET. Cancer Res., 2012, 72(13), 3302-3311.
106. Wang. J. Gui. Z.; Deng, L.; Sun, M.; Guo, R.; Zhang, W.; Shen, L. c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway. Cancer. Lett., 2012, 319, 109-117.
107. Migliore, C.; Martin, V.; Leoni, V.P.;, Restivo, A.; Atzori, L.; Petrelli, A.; Isella, C.; Zorcolo, L/ Sarotto, I.;, Casula, G; Comoglio, P.M.; Columbano, A.; Giordano, S. MiR-1 downregulation cooperates with MACC1 in promoting MET overexpression in human colon cancer. Clin. Cancer Res., 2012, 18, 737-747.