CETUXIMAB: From bench to bedside

Current Cancer Drug Targets

Volumn 10, Issue 1, 2010, Pages 80-95

  Vincenzi, B ^a   Zoccoli, A ^a   Pantano, F ^a   Venditti, O ^a   Galluzzo, S ^a  

^a UNIVERSITY CAMPUS BIO MEDICO   (Italy)

Author keywords

Cetuximab; Epidermal growth factor receptor; Predictive markers; Targeted therapy

Indexed keywords

B RAF KINASE; CETUXIMAB; CISPLATIN; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRINOTECAN; JANUS KINASE; MAGNESIUM; MATRIX METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE; OXALIPLATIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLATINUM; STAT PROTEIN; TOPOTECAN; VASCULOTROPIN;

ANTIANGIOGENIC ACTIVITY; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER RADIOTHERAPY; CANCER SURVIVAL; CARCINOGENESIS; CELL CYCLE ARREST; CLINICAL TRIAL; COLON CANCER; COLORECTAL CANCER; COLORECTAL CARCINOMA; COMPETITIVE INHIBITION; DOSE RESPONSE; DRUG BINDING; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG RESPONSE; DRUG TARGETING; ENZYME INHIBITION; GENE AMPLIFICATION; GENE MUTATION; GROWTH INHIBITION; HEAD AND NECK CARCINOMA; HUMAN; HUMAN CELL; HYPOMAGNESEMIA; IN VITRO STUDY; IN VIVO STUDY; LUNG CANCER; LUNG METASTASIS; LUNG NON SMALL CELL CANCER; LYMPH NODE METASTASIS; METASTASIS; MOLECULAR WEIGHT; MULTIMODALITY CANCER THERAPY; OVARY CANCER; PANCREAS CANCER; PREDICTOR VARIABLE; PROSTATE CANCER; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS INHIBITION; RECEPTOR DOWN REGULATION; REVIEW; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; TUMOR CELL; TUMOR REGRESSION; TUMOR XENOGRAFT;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, SQUAMOUS CELL; CLINICAL TRIALS AS TOPIC; COLORECTAL NEOPLASMS; DRUG RESISTANCE, NEOPLASM; HEAD AND NECK NEOPLASMS; HUMANS; MATRIX METALLOPROTEINASES; MICE; NEOPLASMS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 77950399100     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800910790980241     Document Type: Review

References (154)

1. Mendelsohn, J.; Baselga, J. Epidermal growth factor receptor targeting in cancer. Semin. Oncol. 2006, 33, 369-385.
2. Pérez-Soler, R. HER1/EGFR targeting: refining the strategy. Oncologist 2004, 9, 58-67.
3. Arteaga, C. Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin. Oncol. 2003, 30, 3-14.
4. Baselga, J.; Arteaga, C. L. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J. Clin. Oncol. 2005, 23, 2445-2459.
5. Frienze, D. A.; McCune, J. S. Current status of cetuximab for the treatment of patients with solid tumors. Ann. Pharmacother. 2006, 40, 241-250.
6. Zhang, W.; Gordon, M.; Lenz, H. J. Novel approaches to treatment of advanced colorectal cancer with anti-EGFR monoclonal antibodies. Ann. Med. 2006, 38, 545-551.
7. Goldstein, N. I.; Prewett, M.; Zuklys, K.; Rockwell, P.; Mendelsohn, J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin. Cancer Res. 1995, 1, 1311-1318.
8. Cunningham, D.; Humblet, Y.; Siena, S.; Khayat, D.; Bleiberg, H.; Santoro, A.; Bets, D.; Mueser, M.; Harstrick, A.; Verslype, C.; Chau, I.; Van Cutsem, E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 2004, 351, 337-345.
9. Saltz, L. B.; Meropol, N. J.; Loehrer, P. J. Sr.; Needle, M. N.; Kopit, J.; Mayer, R. J. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J. Clin. Oncol. 2004, 22, 1201-1208.
10. Astsaturov, I.; Cohen, R. B.; Harari, P. M. EGFR-targeting monoclonal antibodies in head and neck cancer. Curr. Cancer Drug Targets 2006, 6, 691-710.
11. Kawamoto, T.; Sato, J. D.; Le, A.; Polikoff, J.; Sato, G. H.; Mendelsohn, J. Growth stimulation of A431 cells by EGF: identification of high affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc. Natl. Acad. Sci. USA 1983, 80, 1337-1341.
12. Sato, J. D.; Kawamoto, T.; Le, A. D.; Mendelsohn, J.; Polikoff, J.; Sato, G. H. Biological effect in vitro of monoclonal antibodies to human EGF receptors. Mol. Biol. Med. 1983, 1, 511-529.
13. Gill, G. N.; Kawamoto, T.; Cochet, C.; Le, A.; Sato, J. D.; Masui, H.; McLeod, C.; Mendelsohn, J. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factorstimulated tyrosine protein kinase activity. J. Biol. Chem. 1984, 259, 7755-7760.
14. Fan, Z.; Baselgam, J.; Masui, H.; Mendelsohn, J. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established a431 cell xenografts. Cancer Res. 1993, 53, 4637-4642.
15. Needle, M. N. Safety experience with IMC-C225, an antiepidermal growth factor receptor antibody. Semin. Oncol. 2002, 29, 55-60.
16. Humblet, Y. Cetuximab: an IgG1 monoclonal antibody for the treatment of epidermal growth factor receptor-expressing tumors. Expert Opin. Pharmacother. 2004, 5, 1621-1633.
17. Herbst, R. S.; Shin, D. M. Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer 2002, 94, 1593-1611.
18. Fan, Z.; Lu, Y.; Wu, X.; Mendelsohn, J. Antibody-induced epidermal growth factor dimerization mediates inhibition of autocrine proliferation of A431 squamous carcinoma cells. J. Biol. Chem. 1994, 269, 27595-27602.
19. Herbst, R. S. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59, 21-26.
20. Burgess, A. W.; Cho, H. S.; Eigenbrot, C.; Ferguson, K. M.; Garrett, T. P.; Leahy, D. J.; Lemmon, M. A.; Sliwkowski, M. X.; Ward, C. W.; Yokoyama, S. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol. Cell. 2003, 12, 541-552.
21. Carpenter, G.; Cohen, S. Epidermal growth factor. J. Biol. Chem. 1990, 265, 7709-7712.
22. Real, F. X.; Rettig, W. J.; Chesa, P. G.; Melamed, M. R.; Old, L. J.; Mendelsohn, J. Expression of epidermal growth factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of differentiation. Cancer Res. 1986, 46, 4726-4731.
23. Olayioye, M. A.; Neve, R. M.; Lane, H. A.; Hynes, N. E. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000, 19, 3159-3167.
24. Harris, R. C.; Chung, E.; Coffey, R. J. EGF receptor ligands. Exp. Cell Res. 2003, 284, 2-13.
25. Sako, Y.; Minoghchi, S.; Yanagida, T. Single-molecule imaging of EGFR signalling on the surface of living cells. Nat. Cell Biol. 2000, 2, 168-172.
26. Waterman, H.; Yarden, Y. Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases. FEBS Lett. 2001, 490, 142-152.
27. Holbro, T.; Hynes, N. E. ErbB receptors: Directing key signaling networks throughout life. Annu. Rev. Pharmacol. Toxicol. 2004, 44, 195-217.
28. Citri, A.; Yarden, Y. EGF-ERBB signalling: Towards the systems level. Nat. Rev. Mol. Cell. Biol. 2006, 7, 505-516.
29. Yarden, Y.; Shilo, B. Z. SnapShot: EGFR signaling pathway. Cell 2007, 131, 1018.
30. Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 2000, 103, 211-225.
31. Alroy, I.; Yarden, Y. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 1997, 410, 83-86.
32. Lewis, T. S.; Shapiro, P. S.; Ahn, N. G. Signal transduction through MAP kinase cascades. Adv. Cancer Res. 1998, 74, 49-139.
33. Muthuswamy, S. K.; Gilman, M.; Brugge, J. S. Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol. Cell Biol. 1999, 19, 6845-6857.
34. Vivanco, I.; Sawyers, C. L. The phosphatidylinositol 3-Kinase-Akt pathway in human cancer. Nat. Rev. Cancer 2002, 2, 489-501.
35. Yarden, Y.; Sliwkowski, M. X. Untangling the ErbB signaling network. Nat. Rev. Mol. Cell Biol. 2001, 2, 127-137.
36. Klapper, L. N.; Kirschbaum, M. H.; Sela, M.; Yarden, Y. Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors. Adv. Cancer Res. 2000, 77, 25-79.
37. Baselga, J. New technologies in EGFR-targeted cancer therapy. Signal. 2000, 1, 12-21.
38. Wells, A. The epidermal growth factor receptor (EGFR)-a new target in cancer therapy. Signal. 2000, 1, 4-11.
39. Salomon, D. S.; Brandt, R.; Ciardiello, F.; Normanno, N. Epidermal growth factor related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol. 1995, 19, 183-232.
40. Meyers, M. B.; Shen, W. P.; Spengler, B. A.; Ciccarone, V.; O'Brien, J. P.; Donner, D. B.; Furth, M. E.; Biedler, J. L. Increased epidermal growth factor receptor in multidrug-resistant human neuroblastoma cells. J. Cell. Biochem. 1988, 38, 87-97.
41. Brabender, J.; Danenberg, K. D.; Metzger, R.; Schneider, P. M.; Park, J.; Salonga, D.; Hölscher, A. H.; Danenberg, P. V. Epidermal growth factor receptor and HER2-neu mRNA expression in nonsmall cell lung cancer is correlated with survival. Clin. Cancer Res. 2001, 7, 1850-1855.
42. Rubin Grandis, J.; Melhem, M. F.; Gooding, W. E.; Day, R.; Holst, V. A.; Wagener, M. M.; Drenning, S. D.; Tweardy, D. J. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J. Natl. Cancer Inst. 1998, 90, 824-832.
43. Rusch, V.; Baselga, J.; Cordon-Cardo, C.; Orazem, J.; Zaman, M.; Hoda, S.; McIntosh, J.; Kurie, J.; Dmitrovsky, E. Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung. Cancer Res. 1993, 53, 2379-2385.
44. Kuan, C. T.; Wikstrand, C. J.; Bigner, D. D. EGF mutant receptor vIII as a molecular target in cancer therapy. Endocr. Relat. Cancer 2001, 8, 83-96.
45. Moscatello, D. K.; Holgado-Madruga, M.; Godwin, A. K.; Ramirez, G.; Gunn, G.; Zoltick, P. W.; Biegel, J. A.; Hayes, R. L.; Wong, A. J. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res. 1995, 55, 5536-5539.
46. Prenzel, N.; Zwick, E.; Daub, H.; Leserer, M.; Abraham, R.; Wallasch, C.; Ullrich, A. EGF receptor transactivation by G-proteincoupled receptors requires metalloproteinase cleavage of proHBEGF. Nature 1999, 402, 884-888.
47. Liu, D.; Aguirre Ghiso, J.; Estrada, Y.; Ossowski, L. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 2002, 1, 445-457.
48. Wu, X.; Fan, Z.; Masui, H.; Rosen, N.; Mendelsohn, J. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J. Clin. Invest. 1995, 95, 1897-1905.
49. Peng, D.; Fan, Z.; Lu, Y.; DeBlasio, T.; Scher, H.; Mendelsohn, J. Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145. Cancer Res. 1996, 56, 3666-3669.
50. Perrotte, P.; Matsumoto, T.; Inoue, K.; Kuniyasu, H.; Eve, B. Y.; Hicklin, D. J.; Radinsky, R.; Dinney, C. P. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin. Cancer Res. 1999, 5, 257-265.
51. Liu, B.; Fang, M.; Lu, Y.; Mendelsohn, J.; Fan, Z. Fibroblast growth factor and insulin-like growth factor differentially modulate the apoptosis and G1 arrest induced by anti-epidermal growth factor receptor monoclonal antibody. Oncogene 2001, 20, 1913-1922.
52. Ciardiello, F.; Bianco, R.; Damiano, V.; De Lorenzo, S.; Pepe, S.; De Placido, S.; Fan, Z.; Mendelsohn, J.; Bianco, A. R.; Tortora, G. Antitumor activity of sequential treatment with topotecan and antiepidermal growth factor receptor monoclonal antibody C225. Clin. Cancer Res. 1999, 5, 909-916.
53. Wu, X.; Rubin, M.; Fan, Z.; DeBlasio, T.; Soos, T.; Koff, A.; Mendelsohn, J. Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody. Oncogene 1996, 12, 1397-1403.
54. Kiyota, A.; Shintani, S.; Mihara, M.; Nakahara, Y.; Ueyama, Y.; Matsumura, T.; Tachikawa, T.; Wong, D. T. Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27(KIP1) and p15(INK4B) and induces G1 arrest in oral squamous carcinoma cell lines. Oncology 2002, 63, 92-98.
55. Sclabas, G. M.; Fujioka, S.; Schmidt, C.; Fan, Z.; Evans, D. B.; Chiao, P. J. Restoring Apoptosis in Pancreatic Cancer Cells by Targeting the Nuclear Factor-κB Signaling Pathway With the Anti-Epidermal Growth Factor Antibody IMC-C225. J. Gastrointest. Surg. 2003, 7, 37-43.
56. Petit, A. M.; Rak, J.; Hung, M. C.; Rockwell, P.; Goldstein, N.; Fendly, B.; Kerbel, R. S. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases downregulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am. J. Pathol. 1997, 151, 1523-1530.
57. Huang, S. M.; Li, J.; Harari, P. M. Molecular Inhibition of Angiogenesis and Metastatic Potential in Human Squamous Cell Carcinomas after Epidermal Growth Factor Receptor Blockade. Mol. Cancer Ther. 2002, 1, 507-514.
58. Böhling, T.; Hatva, E.; Kujala, M.; Claesson-Welsh, L.; Alitalo, K.; Haltia, M. Expression of growth factors and growth factor receptors in capillary hemangioblastoma. J. Neuropathol. Exp. Neurol. 1996, 55, 522-527.
59. Goldman, C. K.; Kim, J.; Wong, W. L.; King, V.; Brock, T.; Gillespie, G. Y. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol. Biol. Cell 1993, 4, 121-133.
60. Bruns, C. J.; Solorzano, C. C.; Harbison, M. T.; Ozawa, S.; Tsan, R.; Fan, D.; Abbruzzese, J.; Traxler, P.; Buchdunger, E.; Radinsky, R.; Fidler, I. J. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 2000, 60, 2926-2935.
61. Kitadai, Y.; Haruma, K.; Sumii, K.; Yamamoto, S.; Ue, T.; Yokozaki, H.; Yasui, W.; Ohmoto, Y.; Kajiyama, G.; Fidler, I. J.; Tahara, E. Expression of interleukin-8 correlates with vascularity in human gastric carcinomas. Am. J. Pathol. 1998, 152, 93-100.
62. Gerber, H. P.; Dixit, V.; Ferrara, N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J. Biol. Chem. 1998, 273, 13313-13316.
63. Ciardiello, F.; Bianco, R.; Damiano, V.; Fontanini, G.; Caputo, R.; Pomatico, G.; De Placido, S.; Bianco, A. R.; Mendelsohn, J.; Tortora, G. Antiangiogenic and Antitumor Activity of Anti- Epidermal Growth Factor Receptor C225 Monoclonal Antibody in Combination with Vascular Endothelial Growth Factor Antisense Oligonucleotide in Human GEO Colon Cancer Cells. Clin. Cancer Res. 2000, 6, 3739-3747.
64. Vincenzi, B.; Santini, D.; Russo, A.; Silletta, M.; Gavasci, M.; Battistoni, F.; Di Cuonzo, G.; Rocci, L.; Gebbia, N.; Tonini, G. Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal cancer patients. Ann. Oncol. 2006, 17, 835-841.
65. Naramura, M.; Gillies, S. D.; Mendelsohn, J.; Reisfeld, R. A.; Mueller, B. M. Therapeutic potential of chimeric and murine anti- (epidermal growth factor receptor) antibodies in a metastasis model for human melanoma. Cancer Immunol. Immunother. 1993, 37, 343-349.
66. Kurai, J.; Chikumi, H.; Hashimoto, K.; Yamaguchi, K.; Yamasaki, A.; Sako, T.; Touge, H.; Makino, H.; Takata, M.; Miyata, M.; Nakamoto, M.; Burioka, N.; Shimizu, E. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin. Cancer Res. 2007, 13, 1552-1561.
67. Kimura, H.; Sakai, K.; Arao, T.; Shimoyama, T.; Tamura, T.; Nishio, K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci. 2007, 98, 1275-1280.
68. Kawaguchi, Y.; Kono, K.; Mimura, K.; Sugai, H.; Akaike, H.; Fujii, H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int. J. Cancer 2007, 120, 781-787.
69. Benhar, M.; Engelberg, D.; Levitzki, A. Cisplatin-induced activation of the EGF receptor. Oncogene 2002, 21, 8723-8731.
70. Van Schaeybroeck, S.; Karaiskou-McCaul, A.; Kelly, D.; Longley, D.; Galligan, L.; Van Cutsem, E.; Johnston, P. Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin. Cancer Res. 2005, 11, 7480-7489.
71. Sumitomo, M.; Asano, T.; Asakuma, J.; Asano, T.; Horiguchi, A.; Hayakawa, M. ZD1839 modulates paclitaxel response in renal cancer by blocking paclitaxel-induced activation of the epidermal growth factor receptor-extracellular signal-regulated kinase pathway. Clin. Cancer Res. 2004, 10, 794-801.
72. Tsang, W.; Song, S.; Kwok, T. Epidermal growth factor induction of resistance to topoisomerase II toxins in human squamous carcinoma A431 cells. Oncol. Rep. 2006, 16, 789-793.
73. Kwok, T.; Sutherland R. Epidermal growth factor reduces resistance to doxorubicin. Int. J. Cancer 1991, 49, 73-76.
74. Baselga, J.; Norton, L.; Masui, H.; Pandiella, A.; Coplan, K.; Miller, W. Epidermal growth factor reduces resistance to doxorubicin. J. Natl. Cancer Inst. 1993, 85, 1327-1333.
75. Prewett, M.; Hooper, A.; Bassi, R.; Ellis, L.; Waksal, H.; Hicklin, D. Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts. Clin. Cancer Res. 2002, 8, 994-1003.
76. Bruns, C.; Harbison, M.; Davis, D.; Portera, C.; Tsan, R.; McConkey, D.; Evans, D. Epidermal growth factor receptor blockage with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin. Cancer Res. 2000, 6, 1936-1948.
77. Liang, K.; Ang, K.; Milas, L.; Hunter, N.; Fan, Z. The epidermal growth factor receptor mediates radioresistance. Int. J. Radiat. Oncol. Biol. Phys. 2003, 57, 246-254.
78. Huang, S. M.; Harari, P. M. Modulation of Radiation Response after Epidermal Growth Factor Receptor Blockade in Squamous Cell Carcinomas: Inhibition of Damage Repair, Cell Cycle Kinetics, and Tumor Angiogenesis. Clin. Cancer Res. 2000, 6, 2166-2174.
79. Bianco, C.; Tortora, G.; Bianco, R.; Caputo, R.; Veneziani, B. M.; Caputo, R.; Damiano,V.; Troiani, T.; Fontanini, G.; Raben, D.; Pepe, S.; Bianco, A. R.; Ciardiello, F. Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). Clin. Cancer Res. 2002, 8, 3250-3258.
80. Bonner, J. A.; Raisch, K. P.; Trummell, H. Q.; Robert, F.; Meredith, R. F.; Spencer, S. A.; Buchsbaum, D. J.; Saleh, M. N.; Stackhouse, M. A.; LoBuglio, A. F.; Peters, G. E.; Carroll, W. R.; Waksal, H. W. Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers. J. Clin. Oncol. 2000, 18, 47S-53S.
81. Milas, L; Mason, K.; Hunter, N.; Petersen, S.; Yamakawa, M.; Ang, K.; Mendelsohn, J.; Fan, Z. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin. Cancer Res. 2000, 6, 701-708.
82. Huang, S. M.; Bock, J. M.; Harari, P. M. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Clin. Cancer Res. 1999, 59, 1935-1940.
83. Dittmann, K.; Mayer, C.; Rodemann, H. P. Inhibition of radiationinduced EGFR nuclear import by C225 (cetuximab) suppresses DNA-PK activity. Radiother. Oncol. 2005, 76, 157-161.
84. Gorski, D. H.; Beckett, M. A.; Jaskowiak, N. T.; Calvin, D. P.; Mauceri, H. J.; Salloum, R. M.; Seetharam, S.; Koons, A.; Hari, D. M.; Kufe, D. W.; Weichselbaum, R. R. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999, 59, 3374-3378.
85. Hess, C.; Vuong, V.; Hegyi, I.; Riesterer, O.; Wood, J.; Fabbro, D.; Glanzmann, C.; Bodis, S.; Pruschy, M. Effect of VEGF receptor inhibitor PTK787/ZK222584 [correction of ZK222548] combined with ionizing radiation on endothelial cells and tumour growth. Br. J. Cancer 2001, 85, 2010-2016.
86. Zips, D.; Eicheler, W.; Geyer, P.; Hessel, F.; Dorfler, A.; Thames, H. D.; Haberey, M.; Baumann, M. Enhanced susceptibility of irradiated tumor vessels to vascular endothelial growth factor receptor tyrosine kinase inhibition. Cancer Res. 2005, 65, 5374-5379.
87. Sobrero, A. F:, Maurel, J.; Fehrenbacher, L.; Scheithauer, W.; Abubakr, Y. A.; Lutz, M. P.; Vega,Villegas, M. E.; Eng, C.; Steinhauer, E. U.; Prausova, J.; Lenz, H. J.; Borg, C.; Middleton, G.; Kröning, H.; Luppi, G.; Kisker, O.; Zubel, A.; Langer, C.; Kopit, J.; Burris, H. A. EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal. J. Clin. Oncol. 2008, 10, 2311-2319.
88. Chung, K. Y.; Shia, J.; Kemeny, N. E.; Shah, M.; Schwartz, G. K.; Tse, A.; Hamilton, A.; Pan, D.; Schrag, D.; Schwartz, L.; Klimstra, D. S.; Fridman, D.; Kelsen, D. P.; Saltz, L. B. Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors That Do Not Express the Epidermal Growth Factor Receptor by Immunohistochemistry. J. Clin. Oncol. 2005, 23, 1803-1810.
89. Vincenzi, B.; Santini, D.; Tonini, G. New issues on cetuximab mechanism of action in epidermal growth factor receptor negative colorectal cancer: the role of vascular endothelial growth factor. J. Clin. Oncol. 2006, 24, 1957.
90. Vincenzi, B.; Santini, D.; Russo, A.; Gavasci, M.; Battistoni, F.; Dicuonzo, G.; Rocci, L.; Rosaria, V. M.; Gebbia, N.; Tonini, G. Circulating VEGF reduction, response and outcome in advanced colorectal cancer patients treated with cetuximab plus irinotecan. Pharmacogenomics 2007, 8, 319-327.
91. Köehne, C.; Zaluski, J.; Chung Rong, C.; Makhson, A.; D'Haens, G.; Pinter, T.; Lim, R.; Ruff, P.; Rougier, P.; Van Cutsem, E. Cetuximab plus FOLFIRI first-line in metastatic colorectal cancer (mCRC): the randomized phase III CRYSTAL trial. Ann. Oncol. (Supplement) 2007, 18, 21.
92. Bokemeyer, C.; Bondarenko, I.; Makhson, A.; Hartmann, J. T.; Aparicio, J.; de Braud, F.; Donea, S.; Ludwig, H.; Schuch, G.; Stroh, C.; Loos, A. H.; Zubel, A.; Koralewski, P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol. 2009, 27, 663-671.
93. Bonner, J. A.; Harari, P. M.; Giralt, J.; Azarnia, N.; Shin, D. M.; Cohen, R. B.; Jones, C. U.; Sur, R.; Raben, D.; Jassem, J.; Ove, R.; Kies, M. S.; Baselga, J.; Youssoufian, H.; Amellal, N.; Rowinsky, E. K.; Ang, K. K. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 2006, 354, 567-578.
94. Vermorken, J. B.; Trigo, J.; Hitt, R.; Koralewski, P.; Diaz-Rubio, E.; Rolland, F.; Knecht, R.; Amellal, N.; Schueler, A.; Baselga, J. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head andneck who failed to respond to platinum-based therapy. J. Clin. Oncol. 2007, 25, 2171-2177.
95. Baselga, J.; Trigo, J. M.; Bourhis, J.; Tortochaux, J.; Cortés-Funes, H.; Hitt, R.; Gascón, P.; Amellal, N.; Harstrick, A.; Eckardt, A. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J. Clin. Oncol. 2005, 23, 5568-5577.
96. Kim, E. S.; Mauer, A. M.; William, W. N. Jr.; Tran, H. T.; Liu, D.; Lee, J. J.; Windt, P.; Hong, W. K.; Vokes, E. E.; Herbst, R. S. A phase 2 study of cetuximab in combination with docetaxel in chemotherapy-refractory/resistant patients with advanced nonsmall cell lung cancer. Cancer 2009, 115(8), 1713-1722.
97. Kim, E. S Cetuximab as a single agent or in combination with chemotherapy in lung cancer. Clin. Lung Cancer 2004, 6, 80-84.
98. Xiong, H. Q.; Rosenberg, A.; LoBuglio, A.; Schmidt, W.; Wolff, R. A.; Deutsch, J.; Needle, M.; James, M.; Abbruzzese, L. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J. Clin. Oncol. 2004, 22, 2610-2616.
99. Cascinu, S.; Berardi, R.; Labianca, R.; Siena, S.; Falcone, A.; Aitini, E.; Barni, S.; Di Costanzo, F.; Dapretto, E.; Tonini, G.; Pierantoni, C.; Artale, S.; Rota, S.; Floriani, I.; Scartozzi, M.; Zaniboni, A. Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial. Lancet Oncol. 2008, 9, 39-44.
100. Motzer, R. J.; Amato, R.; Todd, M.; Hwu, W. J.; Cohen, R.; Baselga, J.; Muss, H.; Cooper, M.; Yu, R.; Ginsberg, M. S.; Needle, M. Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma. Invest. New Drugs 2003, 21, 99-101.
101. Goldstein, N. S.; Armin, M. Epidermal growth factor receptor immunohistochemicalreactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 2001, 92, 1331-1346.
102. Dei Tos, A. P.; Ellis, I. Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods? Eur. J. Cancer 2005, 41, 1383-1392.
103. Kluftinger, A. M.; Robinson, B. W.; Quenville, N. F.; Finley, R. J.; Davis, N. L. Correlation of epidermal growth factor receptor and c erbB2 oncogene product to known prognostic indicators of colorectal cancer. Surg. Oncol. 1992, 1, 97-105.
104. Steele, R. J.; Kelly, P.; Ellul, B.; Eremin, O. Epidermal growth factor receptor expression in colorectal cancer. Br. J. Surg. 1990, 77, 1352-1354.
105. Spano, J. P.; Lagorce, C.; Atlan, D.; Milano, G.; Domont, J.; Benamouzig, R.; Attar, A.; Benichou, J.; Martin, A.; Morere, J. F.; Raphael, M.; Penault-Llorca, F.; Breau, J. L.; Fagard, R.; Khayat, D.; Wind, P. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann. Oncol. 2005, 16, 102-108.
106. Yasui, W.; Sumiyoshi, H.; Hata, J.; Kameda, T.; Ochiai, A.; Ito, H.; Tahara, E. Expression of epidermal growth factor receptor in human gastric and colonic carcinomas. Cancer Res. 1988, 48, 137-141.
107. Koretz, K.; Schlag, P.; Moller, P. Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma. Virchows Arch. 1990, 416, 343-349.
108. Nicholson, R. I.; Gee, J. M.; Harper, M. E. EGFR and cancer prognosis. Eur. J. Cancer 2001, 37, S9-S15.
109. Sargent, D. J.; Conley, B. A.; Allegra, C.; Collette, L. Clinical trial designs for predictive marker validation in cancer treatment trials. J. Clin. Oncol. 2005, 23, 2020-2027.
110. Braun, M. S.; Quirke, P.; Seymour, M. T. Molecular markers of chemotherapeutic response and toxicity in colorectal cancer. Expert Rev. Anticancer Ther. 2007, 7, 489-501.
111. Duffy, M. J. Predictive markers in breast and other cancers: a review. Clin. Chem. 2005, 51, 494-503.
112. Jänne, P. A.; Engelman, J. A.; Johnson, B. E. Epidermal growth factor receptor mutations in non-small-cell lung cancer: Implications for treatment and tumor biology. J. Clin. Oncol. 2005, 23, 3227-3234.
113. Tsuchihashi, Z.; Khambata-Ford, S.; Hanna, N.; Jänne, P. A. Responsiveness to cetuximab without mutations in EGFR. N. Engl. J. Med. 2005, 353, 208-209.
114. Khambata-Ford, S.; Garrett, C. R.; Meropol, N. J.; Basik, M.; Harbison, C. T.; Wu, S.; Wong, T. W.; Huang, X.; Takimoto, C. H.; Godwin, A. K.; Tan, B. R.; Krishnamurthi, S. S.; Burris, H. A.; Poplin, E. A.; Hidalgo, M.; Baselga, J.; Clark, E. A.; Mauro, D. J. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J. Clin. Oncol. 2007, 25, 3230-3237.
115. Scartozzi, M.; Bearzi, I.; Berardi, R.; Mandolesi, A.; Fabris, G.; Cascinu, S. Epidermal Growth Factor Receptor (EGFR) Status in Primary Colorectal Tumors Does Not Correlate With EGFR Expression in Related Metastatic Sites:Implications for Treatment With EGFR-Targeted Monoclonal Antibodies. J. Clin. Oncol. 2004, 22, 4772-4778.
116. McKay, J. A.; Murray, L. J.; Curran, S.; Ross, V. G.; Clark, C.; Murray, G. I.; Cassidy, J.; McLeod, H. L. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur. J. Cancer 2002, 38, 2258-2264.
117. Ellis, L. Epidermal growth factor receptor in tumor angiogenesis. Hematol. Oncol. Clin. North Am. 2004, 18, 1007-1021.
118. Moroni, M.; Veronese, S.; Benvenuti, S.; Marrapese, G.; Sartore-Bianchi, A.; Di Nicolantonio, F.; Gambacorta, M.; Siena, S.; Bardelli, A. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 2005, 6, 279-286.
119. Romagnani, E.; Martin, V.; Ghisletta, M.; Camponovo, A.; Etienne, L.;. Cavalli, F.; Saletti, P.; Mazzucchelli, L.; Frattini, M. EGFR gene status, KRas mutation and PTEN expression predict cetuximab response in metastatic colorectal cancer. Gastrointestinal Cancers Symposium 2007, 427.
120. Lenz, H. J.; Van Cutsem, E.; Khambata-Ford, S.; Mayer, R. J.; Gold, P.; Stella, P.; Mirtsching, B.; Cohn, A. L.; Pippas, A. W.; Azarnia, N.; Tsuchihashi, Z.; Mauro, D. J.; Rowinsky, E. K. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J. Clin. Oncol. 2006, 24, 4914-4921.
121. Lynch, T. J.; Bell, D. W.; Sordella, R.; Gurubhagavatula, S.; Okimoto, R. A.; Brannigan, B. W.; Harris, P. L.; Haserlat, S. M.; Supko, J. G.; Haluska, F. G.; Louis, D. N.; Christiani, D. C.; Settleman, J.; Haber, D. A. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New Engl. J. Med. 2004, 350, 2129-2139.
122. Barber, T. D.; Vogelstein, B.; Kinzler, K. W.; Velculescu, V. E. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N. Engl. J. Med. 2004, 351, 2883.
123. Nagahara, H.; Mimori, K.; Ohta, M.; Utsunomiya, T.; Inoue, H.; Barnard, G. F.; Ohiram, M.; Hirakawa, K.; Mori, M. Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. Clin Cancer Res. 2005, 11, 1368-1371.
124. Ogino, S.; Meyerhardt, J. A.; Cantor, M.; Brahmandam, M.; Clark, J. W.; Namgyal, C.; Kawasaki, T.; Kinsella, K.; Ann, L.; Michelini, A. L.; Enzinger, C. P.; Kulke, H. M.; Ryan, D. P.; Loda, M.; Fuchs, C. S. Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer. Clin. Cancer Res. 2005, 11, 6650-6656.
125. Di Fiore, F.; Blanchard, F.; Charbonnier, F.; Le Pessot, F.; Lamy, A.; Galais, M. P.; Bastit, L.; Killian, A.; Sesboüé, R.; Tuech, J. J.; Queuniet, A. M.; Paillot, B.; Sabourin, J. C.; Michot, F.; Michel, P.; Frebourg, T. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br. J. Cancer 2007, 96, 1166-1169.
126. Personeni, N.; Hendlisz, A.; Gallez, J.; Galdon, M. G.; Larsimont, D.; Van Laethem, J. L.; Nagy, N.; Barette, M.; Paesmans, M.; Cardoso, F.; Bleiberg, H. Correlation between the response to cetuximab alone or in combination with irinotecan and the activated/phosphorylated epidermal growth factor receptor in metastatic colorectal cancer. Semin. Onco. 2005, 32, S59-S62.
127. Chrysogelos, S. A. Chromatin structure of the EGFR gene suggests a role for intron 1 sequences in its regulation in breast cancer cells. Nucleic Acids Res. 1993, 21, 5736.
128. Buerger, H.; Gebhardt, F.; Schmidt, H.; Beckmann, A.; Hutmacher, K.; Simon, R.; Lelle, R.; Boecker, W.; Brandt, B. Length and loss of heterozygosity of an intron 1 polymorphic sequence of egfr is related to cytogenetic alterations and epithelial growth factor receptor expression. Cancer Res. 2000, 60, 854-857.
129. Gebhardt, F.; Zanker, K. S.; Brandt, B. Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1. J. Bio.l Chem. 1999, 274, 13176-13180.
130. Graziano, F.; Ruzzo, A.; Loupakis, F.; Canestrari, E.; Santini, D.; Catalano, V.; Bisonni, R.; Torresi, U.; Floriani, I.; Schiavon, G.; Andreoni, F.; Maltese, P.; Rulli, E.; Humar, B.; Falcone, A.; Giustini, L.; Tonini, G.; Fontana, A.; Masi, G.; Magnani, M. Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer. J. Clin. Oncol. 2008, 9, 27-34.
131. Yamada, M.; Ichikawa, Y.; Yamagishi, S.; Momiyama, N.; Ota, M.; Fujii, S.; Tanaka, K.; Shinji Togo, S.; Shigeo Ohki, S.; Shimada, H. Amphiregulin is a promising prognostic marker for liver metastases of colorectal cancer. Clin. Cancer Res. 2008, 14, 2351-2356.
132. Mutsaers, A. J.; Francia, G.; Man, S.; Lee, C. R.; Ebos, J. M.; Wu, Y.; Witte, L.; Berry, S.; Moore, M.; Kerbel, R. S. Dose-dependent increases in circulating TGF-alpha and other EGFR ligands act as pharmacodynamic markers for optimal biological dosing of cetuximab and are tumor independent. Clin. Cancer Res. 2009, 15, 2397-2405.
133. Malumbres, M.; Barbacid, M. RAS oncogenes: the first 30 years. Nat. Rev. Cancer 2003, 3, 459-465.
134. Lièvre, A.; Bachet, J. B.; Le Corre, D.; Boige, V.; Landi, B.; Emile, J. F.; Côté, J. F.; Tomasic, G.; Penna, C.; Ducreux, M.; Rougier, P.; Penault-Llorca, F.; Laurent-Puig, P. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006, 66, 3992-3995.
135. De Roock, W.; Piessevaux, H.; De Schutter, J.; Janssens, M.; De Hertogh, G.; Personeni, N.; Biesmans, B.; Van Laethem, J. L.; Peeters, M.; Humblet, Y.; Van Cutsem, E.; Tejpar, S. KRAS wildtype state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann. Oncol. 2008, 19, 508-515.
136. Perrone, F.; Lampis, A.; Orsenigo, M.; Di Bartolomeo, M.; Gevorgyan, A.; Losa, M.; Frattini, M.; Riva, C.; Andreola, S.; Bajetta, E.; Bertario, L.; Leo, E.; Pierotti, M. A.; Pilotti, S. PI3KCA/PTEN de regulation contributes to
137. Frattini, M.; Saletti, P.; Romagnani, E.; Martin, V.; Molinari, F.; Ghisletta, M.; Camponovo, A.; Etienne, L. L.; Cavalli, F.; Mazzucchelli, L. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br. J. Cancer 2007, 97, 1139-1145.
138. Camp, E. R.; Summy, J.; Bauer, T. W.; Wenbiao, L.; Gallick, G. E.; Ellis, L. M. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin. Cancer Res. 2005, 11, 397-405.
139. Benvenuti, S.; Sartore-Bianchi, A.; Di Nicolantonio, F.; Zanon, C.; Moroni, M.; Veronese, S.; Siena, S.; Bardelli, A. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007, 67, 2643-2648.
140. Nishi, H.; Neta, G.; Nishi, K.; Akers, L. M.; Rikiyama, T.; Proctor, K. N.; Murphy, B. A.; Johnson, A. C. Analysis of the epidermal growth factor receptor promoter: The effect of nuclear factorkB. Int. J. Mol. Med. 2003, 11, 49-55.
141. Habib, A. A.; Chatterjee, S.; Park, S.; Ratan, R. R.; Lefebvre, S.; Vartanian, T. The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kB (NF-kB)-inducing kinase to activate NF-kB. J. Biol. Chem. 2001, 276, 8865-8874.
142. Hirota, K.; Murata, M.; Itoh, T.; Yodoi, J.; Fukuda, K. Redox sensitive transactivation of epidermal growth factor receptor by tumor necrosis factor confers the NF-kB activation. J. Biol. Chem. 2001, 276, 25953-25958.
143. Scartozzi, M.; Bearzi, I.; Pierantoni, C.; Mandolesi, A.; Loupakis, F.; Zaniboni, A.; Catalano, V.; Quadri, A.; Zorzi, F.; Berardi, R.; Biscotti, T.; Labianca, R.; Falcone, A.; Cascinu, S. Nuclear factor-kB tumor expression predicts response and survival in irinotecanrefractory metastatic colorectal cancer treated with cetuximabirinotecan therapy. J. Clin. Oncol. 2007, 25, 3930-3935.
144. Vallböhmer, D.; Zhang, W.; Gordon, M.; Yang, D. Y.; Yun, J.; Press, O. A.; Rhodes, K. E.; Sherrod, A. E.; Iqbal, S.; Danenberg, K. D.; Groshen, S.; Lenz, H. J. Molecular determinants of cetuximab efficacy. J. Clin. Oncol. 2005, 23, 3536-3544.
145. Schrag, D.; Chung, K. Y.; Flombaum, C.; Saltz, L. Cetuximab therapy and symptomatic hypomagnesemia. J. Natl.Cancer Inst. 2005, 97, 1221-1224.
146. Perrin, C.; Fabre, C.; Raoul, J. L.; Boucher, E. Behavioral disorders secondary to profound hypomagnesemia in a patient given cetuximab for metastatic colorectal cancer hypomagnesemia due to cetuximab treatment. Acta Oncol. 2006, 45, 1135-1136.
147. Fakih, M. G.; Wilding, G.; Lombardo, J. Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clin. Colorectal Cancer 2006, 6, 152-156.
148. Tejpar, S.; Piessevaux, H.; Claes, K.; Piront, P.; Hoenderop, J. G.; Verslype, C.; Van Cutsem, E. Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncol. 2007, 8, 387-394.
149. Fakih, M. Anti-EGFR monoclonal antibody-induced hypomagnesaemia. Lancet Oncol. 2007, 8, 366-367.
150. Wagner, C. A. Disorders of renal magnesium handling explain renal magnesium transport. J. Nephrol. 2007, 20, 507-510.
151. Muallem, S.; Moe, O. W. When EGF is offside, magnesium is wasted. J. Clin. Invest. 2007, 117, 2086-2089.
152. Groenestege, W. M.; Thébault, S.; van der Wijst, J.; van den Berg, D.; Janssen, R.; Tejpar, S.; van den Heuvel, L. P.; van Cutsem, E.; Hoenderop, J. G.; Knoers, N. V.; Bindels, R. J. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J. Clin. Invest. 2007, 117, 2260-2267.
153. Bernardini, D.; Nasulewicz, A.; Mazur, A.; Maier, J. A. Magnesium and microvasculatur endothelial cells: a role in inflammation and angiogenesis. Front. Biosc. 2005, 10, 1177-1182.
154. Lapidos, K. A.; Woodhouse, E. C.; Kohn, E. C.; Masiero, L. Mg++-induced endothelial cell migration: Substratum selectivity and receptor-involvement. Angiogenesis 2001, 4, 21-28.