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The Advancement of Epidermal Growth Factor Receptor Inhibitors in Cancer Therapy

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Apoptosis, Senescence, and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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summary

Epidermal growth factor receptor (EGFR) signaling is involved in various cellular processes ranging from normal growth and differentiation to oncogenesis. Targeted disruption of this pathway affords therapeutic potential in oncology, particularly in combination with conventional anticancer treatment modalities. Preclinical data across a spectrum of tumor model systems show promise for this approach, and a broad series of clinical trials that examine EGFR inhibition are currently underway or recently complete. Insights gained from early preclinical and clinical experience regarding mechanisms of EGFR action and response to inhibitors are helping to shape the rational incorporation of these new agents into modern cancer therapy.

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References

  1. Gill GN, Kawamoto T, Cochet C, etal. Monoclonal anti-epidermala growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. JBiol Chem 1984; 259, 7755–7760.

    CAS  Google Scholar 

  2. Kim ES, Khuri FR, Herbst RS. Epidermal growth factor receptor biology (IMC-C225). Curr Opin Oncol 2001; 13, 506–513.

    PubMed  CAS  Google Scholar 

  3. Bonner JA, Harari PM, Giralt J, etal. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006; 354, 567–578.

    PubMed  CAS  Google Scholar 

  4. Saltz L, Rubin M, Hochster H, etal. Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc Am Soc Clin Oncol 2001; 20, Abstract7.

    Google Scholar 

  5. Shepherd F, Pereira J, Ciuleanu E, etal. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proc Am Soc Clin Oncol 2004; 22,7022.

    Google Scholar 

  6. Cohen S, Carpenter G. Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci USA 1975; 72, 1317–1321.

    PubMed  CAS  Google Scholar 

  7. Ullrich A, Coussens L, Hayflick JS, etal. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 1984; 309, 418–425.

    PubMed  CAS  Google Scholar 

  8. Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem 1990; 265, 7709–7712.

    PubMed  CAS  Google Scholar 

  9. Wells A. EGF receptor. Int J Biochem Cell Biol 1999; 31, 637–643.

    PubMed  CAS  Google Scholar 

  10. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000; 19, 3159–3167.

    PubMed  CAS  Google Scholar 

  11. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2, 127–137.

    PubMed  CAS  Google Scholar 

  12. Toyoda H, Komurasaki T, Uchida D, Morimoto S. Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. Biochem J 1997; 326,69–75.

    PubMed  CAS  Google Scholar 

  13. Watanabe T, Shintani A, Nakata M, etal. Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction. J Biol Chem 1994; 269, 9966–9973.

    PubMed  CAS  Google Scholar 

  14. Bogdan S, Klambt C. Epidermal growth factor receptor signaling. Curr Biol 2001; 11, R292–R295.

    PubMed  CAS  Google Scholar 

  15. Moghal N, Sternberg PW. Multiple positive and negative regulators of signaling by the EGF-receptor. Curr Opin Cell Biol 1999; 11, 190–196.

    PubMed  CAS  Google Scholar 

  16. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005; 5, 341–354.

    PubMed  CAS  Google Scholar 

  17. Marmor MD, Skaria KB, Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors. Int J Radiat Oncol Biol Phys 2004; 58, 903–913.

    PubMed  CAS  Google Scholar 

  18. Lenferink AE, Pinkas-Kramarski R, van de Poll ML, etal. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J 1998; 17, 3385–3397.

    PubMed  CAS  Google Scholar 

  19. Worthylake R, Opresko LK, Wiley HS. ErbB-2 amplification inhibits down-regulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 1999; 274, 8865–8874.

    PubMed  CAS  Google Scholar 

  20. Beerli RR, Hynes NE. Epidermal growth factor-related peptides activate distinct subsets of ErbB receptors and differ in their biological activities. J Biol Chem 1996; 271, 6071–6076.

    PubMed  CAS  Google Scholar 

  21. French AR, Tadaki DK, Niyogi SK, Lauffenburger DA. Intracellular trafficking of epidermal growth factor family ligands is directly influenced by the pH sensitivity of the receptor/ligand interaction. J Biol Chem 1995; 270, 4334–4340.

    PubMed  CAS  Google Scholar 

  22. 2Riese DJ 2nd, Bermingham Y, van Raaij TM, Buckley S, Plowman GD, Stern DF. Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta. Oncogene 1996; 12, 345–353.

    PubMed  CAS  Google Scholar 

  23. Tzahar E, Moyer JD, Waterman H, etal. Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network. EMBO J 1998; 17, 5948–5963.

    PubMed  CAS  Google Scholar 

  24. Waterman H, Sabanai I, Geiger B, Yarden Y. Alternative intracellular routing of ErbB receptors may determine signaling potency. J Biol Chem 1998; 273, 13819–13827.

    PubMed  CAS  Google Scholar 

  25. Carpenter G. The EGF receptor: a nexus for trafficking and signaling. Bioessays 2000; 22, 697–707.

    PubMed  CAS  Google Scholar 

  26. Grant S, Qiao L, Dent P. Roles of ERBB family receptor tyrosine kinases, and downstream signaling pathways, in the control of cell growth and survival. Front Biosci 2002; 7, d376–d389.

    PubMed  CAS  Google Scholar 

  27. Salomon DS, 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.

    PubMed  CAS  Google Scholar 

  28. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999; 82, 241–250.

    PubMed  CAS  Google Scholar 

  29. Moscatello DK, Montgomery RB, Sundareshan P, McDanel H, Wong MY, Wong AJ. Transformational and altered signal transduction by a naturally occurring mutant EGF receptor. Oncogene 1996; 13,85–96.

    PubMed  CAS  Google Scholar 

  30. Rasheed BK, Wiltshire RN, Bigner SH, Bigner DD. Molecular pathogenesis of malignant gliomas. Curr Opin Oncol 1999; 11, 162–167.

    PubMed  CAS  Google Scholar 

  31. Arteaga CL. Epidermal growth factor receptor dependence in human tumors: more than just expression? Oncologist 2002; 7 Suppl 4,31–39.

    Google Scholar 

  32. Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001; 37 Suppl 4, S9–S15.

    Google Scholar 

  33. Aaronson SA. Growth factors and cancer. Science 1991; 254, 1146–1153.

    PubMed  CAS  Google Scholar 

  34. Earp HS 3rd, Calvo BF, Sartor CI. The EGF receptor family– multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4. Trans Am Clin Climatol Assoc 2003; 114, 315–333; discussion 333–334.

    PubMed  Google Scholar 

  35. Grunwald V, Hidalgo M. Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 2003; 95, 851–867.

    PubMed  Google Scholar 

  36. Bishop PC, Myers T, Robey R, etal. Differential sensitivity of cancer cells to inhibitors of the epidermal growth factor receptor family. Oncogene 2002; 21, 119–127.

    PubMed  CAS  Google Scholar 

  37. Giordano A, Rustum YM, Wenner CE. Cell cycle: molecular targets for diagnosis and therapy: tumor suppressor genes and cell cycle progression in cancer. J Cell Biochem 1998; 70,1–7.

    PubMed  CAS  Google Scholar 

  38. Anderson NG, Ahmad T, Chan K, Dobson R, Bundred NJ. ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression. Int J Cancer 2001; 94, 774–782.

    PubMed  CAS  Google Scholar 

  39. Chan KC, Knox WF, Gandhi A, Slamon DJ, Potten CS, Bundred NJ. Blockade of growth factor receptors in ductal carcinoma in situ inhibits epithelial proliferation. Br J Surg 2001; 88, 412–418.

    PubMed  CAS  Google Scholar 

  40. Huang SM, Li J, Armstrong EA, Harari PM. Modulation of radiation response and tumor-induced angiogenesis after epidermal growth factor receptor inhibition by ZD1839 (Iressa). Cancer Res 2002; 62, 4300–4306.

    PubMed  CAS  Google Scholar 

  41. Kiyota A, Shintani S, Mihara M, etal. 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.

    PubMed  CAS  Google Scholar 

  42. Lichtner RB, Menrad A, Sommer A, Klar U, Schneider MR. Signaling-inactive epidermal growth factor receptor/ligand complexes in intact carcinoma cells by quinazoline tyrosine kinase inhibitors. Cancer Res 2001; 61, 5790–5795.

    PubMed  CAS  Google Scholar 

  43. 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.

    PubMed  CAS  Google Scholar 

  44. Shintani S, Li C, Mihara M, etal. Gefitinib (‘Iressa’, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, up-regulates p27KIP1 and induces G1 arrest in oral squamous cell carcinoma cell lines. Oral Oncol 2004; 40,43–51.

    PubMed  CAS  Google Scholar 

  45. Wu X, Rubin M, Fan Z, etal. Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody. Oncogene 1996; 12, 1397–1403.

    PubMed  CAS  Google Scholar 

  46. Huang SM, Bock JM, Harari PM. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 1999; 59, 1935–1940.

    PubMed  CAS  Google Scholar 

  47. Raben D, Helfrich BA, Chan D, Johnson G, Bunn PAJ. ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer. Semin Oncol 2002; 29,37–46.

    PubMed  CAS  Google Scholar 

  48. Perrotte P, Matsumoto T, Inoue K, etal. 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.

    PubMed  CAS  Google Scholar 

  49. Chang GC, Hsu SL, Tsai JR, etal. Molecular mechanisms of ZD1839-induced G1-cell cycle arrest and apoptosis in human lung adenocarcinoma A549 cells. Biochem Pharmacol 2004; 68, 1453–1464.

    PubMed  CAS  Google Scholar 

  50. Gibson EM, Henson ES, Haney N, Villanueva J, Gibson SB. Epidermal growth factor protects epithelial-derived cells from tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by inhibiting cytochrome c release. Cancer Res 2002; 62, 488–496.

    PubMed  CAS  Google Scholar 

  51. Gibson S, Tu S, Oyer R, Anderson SM, Johnson GL. Epidermal growth factor protects epithelial cells against Fas-induced apoptosis. Requirement for Akt activation. J Biol Chem 1999; 274, 17612–17618.

    PubMed  CAS  Google Scholar 

  52. Takeuchi K, Ito F. Suppression of adriamycin-induced apoptosis by sustained activation of the phosphatidylinositol-3′-OH kinase-Akt pathway. J Biol Chem 2004; 279, 892–900.

    PubMed  CAS  Google Scholar 

  53. Ramljak D, Coticchia CM, Nishanian TG, etal. Epidermal growth factor inhibition of c-Myc-mediated apoptosis through Akt and Erk involves Bcl-xL upregulation in mammary epithelial cells. Exp Cell Res 2003; 287, 397–410.

    PubMed  CAS  Google Scholar 

  54. Modjtahedi H, Affleck K, Stubberfield C, Dean C. EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5. Int J Oncol 1998; 13, 335–342.

    PubMed  CAS  Google Scholar 

  55. 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.

    PubMed  CAS  Google Scholar 

  56. Gilmore AP, Valentijn AJ, Wang P, etal. Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem 2002; 277, 27643–27650.

    PubMed  CAS  Google Scholar 

  57. Karnes WEJ, Weller SG, Adjei PN, etal. Inhibition of epidermal growth factor receptor kinase induces protease-dependent apoptosis in human colon cancer cells. Gastroenterology 1998; 114, 930–939.

    PubMed  CAS  Google Scholar 

  58. Moyer JD, Barbacci EG, Iwata KK, etal. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res 1997; 57, 4838–4848.

    PubMed  CAS  Google Scholar 

  59. Huang S, Armstrong EA, Benavente S, Chinnaiyan P, Harari PM. Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res 2004; 64, 5355–5362.

    PubMed  CAS  Google Scholar 

  60. Matar P, Rojo F, Cassia R, etal. Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting. Clin Cancer Res 2004; 10, 6487–6501.

    PubMed  CAS  Google Scholar 

  61. Jost M, Class R, Kari C, Jensen PJ, Rodeck U. A central role of Bcl-X(L) in the regulation of keratinocyte survival by autocrine EGFR ligands. J Invest Dermatol 1999; 112, 443–449.

    PubMed  CAS  Google Scholar 

  62. Mandal M, Adam L, Mendelsohn J, Kumar R. Nuclear targeting of Bax during apoptosis in human colorectal cancer cells. Oncogene 1998; 17, 999–1007.

    PubMed  CAS  Google Scholar 

  63. Tortora G, Caputo R, Damiano V, etal. Combined targeted inhibition of bcl-2, bcl-XL, epidermal growth factor receptor, and protein kinase A type I causes potent antitumor, apoptotic, and antiangiogenic activity. Clin Cancer Res 2003; 9, 866–871.

    PubMed  CAS  Google Scholar 

  64. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285, 1182–1186.

    PubMed  CAS  Google Scholar 

  65. Bouma-ter Steege JC, Mayo KH, Griffioen AW. Angiostatic proteins and peptides. Crit Rev Eukaryot Gene Expr 2001; 11, 319–334.

    PubMed  CAS  Google Scholar 

  66. Eisma RJ, Spiro JD, Kreutzer DL. Role of angiogenic factors: coexpression of interleukin-8 and vascular endothelial growth factor in patients with head and neck squamous carcinoma. Laryngoscope 1999; 109, 687–693.

    PubMed  CAS  Google Scholar 

  67. Fox SB, Gatter KC, Harris AL. Tumour angiogenesis. J Pathol 1996; 179, 232–237.

    PubMed  CAS  Google Scholar 

  68. Shemirani B, Crowe DL. Head and neck squamous cell carcinoma lines produce biologically active angiogenic factors. Oral Oncol 2000; 36,61–66.

    PubMed  CAS  Google Scholar 

  69. Smith BD, Haffty BG, Sasaki CT. Molecular markers in head and neck squamous cell carcinoma: their biological function and prognostic significance. Ann Otol Rhinol Laryngol 2001; 110, 221–228.

    PubMed  CAS  Google Scholar 

  70. Ellis LM. Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am 2004; 18, 1007–21,viii.

    PubMed  Google Scholar 

  71. Harris VK, Coticchia CM, Kagan BL, Ahmad S, Wellstein A, Riegel AT. Induction of the angiogenic modulator fibroblast growth factor-binding protein by epidermal growth factor is mediated through both MEK/ERK and p38 signal transduction pathways. J Biol Chem 2000; 275, 10802–10811.

    PubMed  CAS  Google Scholar 

  72. Huang SM, Li J, Harari PM. 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.

    PubMed  CAS  Google Scholar 

  73. Petit AM, Rak J, Hung MC, etal. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells invitro and invivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997; 151, 1523–1530.

    PubMed  CAS  Google Scholar 

  74. Kim SJ, Uehara H, Karashima T, Shepherd DL, Killion JJ, Fidler IJ. Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice. Clin Cancer Res 2003; 9, 1200–1210.

    PubMed  CAS  Google Scholar 

  75. Schreiber AB, Winkler ME, Derynck R. Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science 1986; 232, 1250–1253.

    PubMed  CAS  Google Scholar 

  76. Bancroft CC, Chen Z, Yeh J, etal. Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines. Int J Cancer 2002; 99, 538–548.

    PubMed  CAS  Google Scholar 

  77. O-charoenrat P, Rhys-Evans P, Modjtahedi H, Eccles SA. Vascular endothelial growth factor family members are differentially regulated by c-erbB signaling in head and neck squamous carcinoma cells. Clin Exp Metastasis 2000; 18, 155–161.

    PubMed  CAS  Google Scholar 

  78. O-charoenrat P, Rhys-Evans PH, Archer DJ, Eccles SA. C-erbB receptors in squamous cell carcinomas of the head and neck: clinical significance and correlation with matrix metalloproteinases and vascular endothelial growth factors. Oral Oncol 2002; 38,73–80.

    PubMed  CAS  Google Scholar 

  79. Ravindranath N, Wion D, Brachet P, Djakiew D. Epidermal growth factor modulates the expression of vascular endothelial growth factor in the human prostate. J Androl 2001; 22, 432–443.

    PubMed  CAS  Google Scholar 

  80. Gille J, Swerlick RA, Caughman SW. Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. EMBO J 1997; 16, 750–759.

    PubMed  CAS  Google Scholar 

  81. Ciardiello F, Caputo R, Bianco R, etal. Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res 2001; 7, 1459–1465.

    PubMed  CAS  Google Scholar 

  82. Hirata A, Ogawa S, Kometani T, etal. ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 2002; 62, 2554–2560.

    PubMed  CAS  Google Scholar 

  83. Huang SM, Harari PM. 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.

    PubMed  CAS  Google Scholar 

  84. Helliwell TR. Molecular markers of metastasis in squamous carcinomas. J Pathol 2001; 194, 289–293.

    Google Scholar 

  85. Juarez J, Clayman G, Nakajima M, etal. Role and regulation of expression of 92-kDa type-IV collagenase (MMP-9) in 2 invasive squamous-cell-carcinoma cell lines of the oral cavity. IntJCancer 1993; 55,10–18.

    CAS  Google Scholar 

  86. Kusukawa J, Harada H, Shima I, Sasaguri Y, Kameyama T, Morimatsu M. The significance of epidermal growth factor receptor and matrix metalloproteinase-3 in squamous cell carcinoma of the oral cavity. Eur J Cancer B Oral Oncol 1996; 32B, 217–221.

    PubMed  CAS  Google Scholar 

  87. O-charoenrat P, Modjtahedi H, Rhys-Evans P, Court WJ, Box GM, Eccles SA. Epidermal growth factor-like ligands differentially up-regulate matrix metalloproteinase 9 in head and neck squamous carcinoma cells. Cancer Res 2000; 60, 1121–1128.

    PubMed  CAS  Google Scholar 

  88. Quon H, Liu FF, Cummings BJ. Potential molecular prognostic markers in head and neck squamous cell carcinomas. Head Neck 2001; 23, 147–159.

    PubMed  CAS  Google Scholar 

  89. Price JT, Wilson HM, Haites NE. Epidermal growth factor (EGF) increases the invitro invasion, motility and adhesion interactions of the primary renal carcinoma cell line, A704. Eur J Cancer 1996; 32A, 1977–1982.

    PubMed  CAS  Google Scholar 

  90. Wyckoff J, Wang W, Lin EY, etal. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 2004; 64, 7022–7029.

    PubMed  CAS  Google Scholar 

  91. Mamoune A, Kassis J, Kharait S, etal. DU145 human prostate carcinoma invasiveness is modulated by urokinase receptor (uPAR) downstream of epidermal growth factor receptor (EGFR) signaling. Exp Cell Res 2004; 299, 91–100.

    PubMed  CAS  Google Scholar 

  92. Kruger JS, Reddy KB. Distinct mechanisms mediate the initial and sustained phases of cell migration in epidermal growth factor receptor-overexpressing cells. Mol Cancer Res 2003; 1, 801–809.

    PubMed  CAS  Google Scholar 

  93. O-charoenrat P, Wongkajornsilp A, Rhys-Evans PH, Eccles SA. Signaling pathways required for matrix metalloproteinase-9 induction by betacellulin in head-and-neck squamous carcinoma cells. Int J Cancer 2004; 111, 174–183.

    PubMed  CAS  Google Scholar 

  94. Bruns CJ, Harbison MT, Davis DW, etal. Epidermal growth factor receptor blockade 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.

    PubMed  CAS  Google Scholar 

  95. Contessa JN, Reardon DB, Todd D, etal. The inducible expression of dominant-negative epidermal growth factor receptor-CD533 results in radiosensitization of human mammary carcinoma cells. Clin Cancer Res 1999; 5, 405–411.

    PubMed  CAS  Google Scholar 

  96. Sheridan MT, O’Dwyer T, Seymour CB, Mothersill CE. Potential indicators of radiosensitivity in squamous cell carcinoma of the head and neck. Radiat Oncol Investig 1997; 5, 180–186.

    PubMed  CAS  Google Scholar 

  97. Zhu A, Shaeffer J, Leslie S, Kolm P, El-Mahdi AM. Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation. Int J Radiat Oncol Biol Phys 1996; 34, 809–815.

    PubMed  CAS  Google Scholar 

  98. Bonner JA, Buchsbaum DJ, Rogers BE, etal. Adenoviral vector-mediated augmentation of epidermal growth factor receptor (EGFr) enhances the radiosensitization properties of anti-EGFr treatment in prostate cancer cells. Int J Radiat Oncol Biol Phys 2004; 58, 950–958.

    PubMed  CAS  Google Scholar 

  99. Bonner JA, Buchsbaum DJ, Russo SM, etal. Anti-EGFR-mediated radiosensitization as a result of augmented EGFR expression. Int J Radiat Oncol Biol Phys 2004; 59,2–10.

    PubMed  CAS  Google Scholar 

  100. Liang K, Ang KK, Milas L, Hunter N, Fan Z. The epidermal growth factor receptor mediates radioresistance. Int J Radiat Oncol Biol Phys 2003; 57, 246–254.

    PubMed  CAS  Google Scholar 

  101. Akimoto T, Hunter NR, Buchmiller L, Mason K, Ang KK, Milas L. Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas. Clin Cancer Res 1999; 5, 2884–2890.

    PubMed  CAS  Google Scholar 

  102. Kavanagh BD, Lin PS, Chen P, Schmidt-Ullrich RK. Radiation-induced enhanced proliferation of human squamous cancer cells invitro: a release from inhibition by epidermal growth factor. Clin Cancer Res 1995; 1, 1557–1562.

    PubMed  CAS  Google Scholar 

  103. Schmidt-Ullrich RK, Mikkelsen RB, Dent P, etal. Radiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 1997; 15, 1191–1197.

    PubMed  CAS  Google Scholar 

  104. Lammering G, Hewit TH, Valerie K, etal. EGFRvIII-mediated radioresistance through a strong cytoprotective response. Oncogene 2003; 22, 5545–5553.

    PubMed  CAS  Google Scholar 

  105. Balaban N, Moni J, Shannon M, Dang L, Murphy E, Goldkorn T. The effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation. Biochim Biophys Acta 1996; 1314, 147–156.

    PubMed  CAS  Google Scholar 

  106. Nasu S, Ang KK, Fan Z, Milas L. C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability. Int J Radiat Oncol Biol Phys 2001; 51, 474–477.

    PubMed  CAS  Google Scholar 

  107. Solomon B, Hagekyriakou J, Trivett MK, Stacker SA, McArthur GA, Cullinane C. EGFR blockade with ZD1839 (“Iressa”) potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cell carcinoma. Epidermal growth factor receptor. Int J Radiat Oncol Biol Phys 2003; 55, 713–723.

    PubMed  CAS  Google Scholar 

  108. Zhou H, Kim YS, Peletier A, McCall W, Earp HS, Sartor CI. Effects of the EGFR/HER2 kinase inhibitor GW572016 on EGFR- and HER2-overexpressing breast cancer cell line proliferation, radiosensitization, and resistance. Int J Radiat Oncol Biol Phys 2004; 58, 344–352.

    PubMed  CAS  Google Scholar 

  109. Akimoto T, Nonaka T, Harashima K, Ishikawa H, Sakurai H, Mitsuhashi N. Selective inhibition of survival signal transduction pathways enhanced radiosensitivity in human esophageal cancer cell lines invitro. Anticancer Res 2004; 24, 811–819.

    PubMed  CAS  Google Scholar 

  110. Bonner JA, Raisch KP, Trummell HQ, etal. 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.

    PubMed  CAS  Google Scholar 

  111. Milas L, Mason K, Hunter N, etal. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res 2000; 6, 701–708.

    PubMed  CAS  Google Scholar 

  112. Nakata E, Hunter N, Mason K, Fan Z, Ang KK, Milas L. C225 antiepidermal growth factor receptor antibody enhances the efficacy of docetaxel chemoradiotherapy. Int J Radiat Oncol Biol Phys 2004; 59, 1163–1173.

    PubMed  CAS  Google Scholar 

  113. She Y, Lee F, Chen J, etal. The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index. Clin Cancer Res 2003; 9, 3773–3778.

    PubMed  CAS  Google Scholar 

  114. Williams KJ, Telfer BA, Stratford IJ, Wedge SR. ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model. Br J Cancer 2002; 86, 1157–1161.

    PubMed  CAS  Google Scholar 

  115. Chinnaiyan P, Huang S, Vallabhaneni G, etal. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res 2005; 65, 3328–3335.

    PubMed  CAS  Google Scholar 

  116. Ciardiello F, Bianco R, Damiano V, etal. Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. Clin Cancer Res 1999; 5, 909–916.

    PubMed  CAS  Google Scholar 

  117. Fan Z, Baselga 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.

    PubMed  CAS  Google Scholar 

  118. Inoue K, Slaton JW, Perrotte P, etal. Paclitaxel enhances the effects of the anti-epidermal growth factor receptor monoclonal antibody ImClone C225 in mice with metastatic human bladder transitional cell carcinoma. Clin Cancer Res 2000; 6, 4874–4884.

    PubMed  CAS  Google Scholar 

  119. Mendelsohn J, Fan Z. Epidermal growth factor receptor family and chemosensitization. J Natl Cancer Inst 1997; 89, 341–343.

    PubMed  CAS  Google Scholar 

  120. Prewett MC, Hooper AT, Bassi R, Ellis LM, Waksal HW, Hicklin DJ. 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.

    PubMed  CAS  Google Scholar 

  121. Shin DM, Donato NJ, Perez-Soler R, etal. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 2001; 7, 1204–1213.

    PubMed  CAS  Google Scholar 

  122. Ciardiello F, Caputo R, Bianco R, etal. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000; 6, 2053–2063.

    PubMed  CAS  Google Scholar 

  123. Sirotnak FM, Zakowski MF, Miller VA, Scher HI, Kris MG. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res 2000; 6, 4885–4892.

    PubMed  CAS  Google Scholar 

  124. Bundred NJ, Chan K, Anderson NG. Studies of epidermal growth factor receptor inhibition in breast cancer. Endocr Relat Cancer 2001; 8, 183–189.

    PubMed  CAS  Google Scholar 

  125. Ling YH, Donato NJ, Perez-Soler R. Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines. Cancer Chemother Pharmacol 2001; 47, 473–480.

    PubMed  CAS  Google Scholar 

  126. Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF, Arteaga CL. Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells invitro and invivo. Cancer Res 2001; 61, 8887–8895.

    PubMed  CAS  Google Scholar 

  127. Higgins B, Kolinsky K, Smith M, etal. Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models. Anticancer Drugs 2004; 15, 503–512.

    PubMed  CAS  Google Scholar 

  128. Ng SS, Tsao MS, Nicklee T, Hedley DW. Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol Cancer Ther 2002; 1, 777–783.

    PubMed  CAS  Google Scholar 

  129. Pollack VA, Savage DM, Baker DA, etal. Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J Pharmacol Exp Ther 1999; 291, 739–748.

    PubMed  CAS  Google Scholar 

  130. Warburton C, Dragowska WH, Gelmon K, etal. Treatment of HER-2/neu overexpressing breast cancer xenograft models with trastuzumab (Herceptin) and gefitinib (ZD1839): drug combination effects on tumor growth, HER-2/neu and epidermal growth factor receptor expression, and viable hypoxic cell fraction. Clin Cancer Res 2004; 10, 2512–2524.

    PubMed  CAS  Google Scholar 

  131. Formento P, Hannoun-Levi JM, Fischel JL, Magne N, Etienne-Grimaldi MC, Milano G. Dual HER 1–2 targeting of hormone-refractory prostate cancer by ZD1839 and trastuzumab. Eur J Cancer 2004; 40, 2837–2844.

    PubMed  CAS  Google Scholar 

  132. Kuwada SK, Scaife CL, Kuang J, etal. Effects of trastuzumab on epidermal growth factor receptor-dependent and -independent human colon cancer cells. Int J Cancer 2004; 109, 291–301.

    PubMed  CAS  Google Scholar 

  133. Xia W, Mullin RJ, Keith BR, etal. Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 2002; 21, 6255–6263.

    PubMed  CAS  Google Scholar 

  134. Traxler P, Allegrini PR, Brandt R, etal. AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 2004; 64, 4931–4941.

    PubMed  CAS  Google Scholar 

  135. Yigitbasi OG, Younes MN, Doan D, etal. Tumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade. Cancer Res 2004; 64, 7977–7984.

    PubMed  CAS  Google Scholar 

  136. Ciardiello F, Caputo R, Damiano V, etal. Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin Cancer Res 2003; 9, 1546–1556.

    PubMed  CAS  Google Scholar 

  137. Wedge SR, Ogilvie DJ, Dukes M, etal. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res 2002; 62, 4645–4655.

    PubMed  CAS  Google Scholar 

  138. Kim SJ, Uehara H, Yazici S, etal. Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice. Cancer Res 2004; 64, 4201–4208.

    PubMed  CAS  Google Scholar 

  139. Burtrum D, Zhu Z, Lu D, etal. A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Res 2003; 63, 8912–8921.

    PubMed  CAS  Google Scholar 

  140. Goetsch L, Gonzalez A, Leger O, etal. A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts. Int J Cancer 2005; 113, 316–328.

    PubMed  CAS  Google Scholar 

  141. Grandis JR, Drenning SD, Chakraborty A, etal. Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth invitro. J Clin Invest 1998; 102, 1385–1392.

    PubMed  CAS  Google Scholar 

  142. Lo HW, Hsu SC, Ali-Seyed M, etal. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 2005; 7, 575–589.

    PubMed  CAS  Google Scholar 

  143. Benavente S, Armstrong E, Hsu KT, Huang S, Harari PM. Array-based identification of genes and proteins associated with resistance to EGFR inhibitors. AACR 2006; 1, Abstract1246.

    Google Scholar 

  144. Gondi V, Huang S, Benavente S, Armstrong E, Harari PM. Potential mechanisms of acquired resistance to EGFR inhibitors. AACR 2006; 1, Abstract1244.

    Google Scholar 

  145. Kelly K, Hanna N, Rosenberg A, Bunn PAJ. A multicenter phase I/II study of cetuximab in combination with paclitaxel and carboplatin in untreated patients with stage IV non-small cell lung cancer. Proc Am Soc Clin Oncol 2003; 22,2592.

    Google Scholar 

  146. Robert F, Blumenschein G, Dicke K, Tseng J, Saleh MN. Phase IB/IIA study of anti-epidermal growth factor receptor antibody, cetuximab, in combination with gemcitabine/carboplatin in patients with advanced stage IV non-small cell lung cancer. Proc Am Soc Clin Oncol 2003; 22,2587.

    Google Scholar 

  147. Saltz LB, Meropol NJ, Loehrer PJS, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. JClin Oncol 2004; 22, 1201–1208.

    CAS  Google Scholar 

  148. Vega-Villegas E, Awada R, Mesia L, Geoffrois L, Borel C. A phase I study of cetuximab in combination with cisplatin or carboplatin and 5-FU in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Proc Am Assoc Cancer Res 2003; 22,2020.

    Google Scholar 

  149. Cunningham D, Humblet Y, Siena D, etal. Cetuximab (C225) alone or in combination with irinotecan (CPT-11) in patients with epidermal growth factor receptor (EGFR)-positive, irinotecan-refractory metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol 2003; 22, Abstract1012.

    Google Scholar 

  150. Wang P, Fredlin P, Davis CG, Yang X-D. Human anti-EGF receptor monoclonal antibody ABX-EGF: a potential monotherapy for the treatment of prostate cancer. Proc Am Soc Clin Oncol 2003; 22, Abstract4525.

    Google Scholar 

  151. Meropol NJ, Berlin J, Hecht JR, etal. Multicenter study of ABX-EGF monotherapy in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 2003; 22, Abstract1026.

    Google Scholar 

  152. Woodburn JR, Kendrew J, Fennell M, Wakeling AE. ZD1839 (‘IRESSA’), a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI): inhibition of c-fos mRNA, an intermediate marker of EGFR activation, correlates with tumor growth inhibition. Proc Am Assoc Cancer Res 2000; 41, Abstract2552.

    Google Scholar 

  153. Arteaga CL, Johnson DH. Tyrosine kinase inhibitors-ZD1839 (Iressa). Curr Opin Oncol 2001; 13, 491–498.

    PubMed  CAS  Google Scholar 

  154. Baselga J, Albanell J, Ruiz A, etal. Phase II and tumor pharmacodynamic study of gefitinib (ZD1839) in patients with advanced breast cancer. Proc Am Soc Clin Oncol 2003; 22, Abstract24.

    Google Scholar 

  155. Cohen EE, Stenson K, Gustin DM, etal. A phase II study of 250-mg gefitinib (ZD1839) monotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proc Am Soc Clin Oncol 2003; 22, Abstract2021.

    Google Scholar 

  156. Cohen EE, Rosen F, Dekker A, etal. Phase II study of ZD1839 (Iressa) in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proc Am Soc Clin Oncol 2002; 21, Abstract899.

    Google Scholar 

  157. Dawson NA, Guo C, Zak R, etal. A phase II trial of ZD1839 in stage IV and recurrent renal cell carcinoma. Proc Am Soc Clin Oncol 2003; 22, Abstract1623.

    Google Scholar 

  158. Fountzilas G, Pectasides D, Skarlos DV, etal. Paclitaxel, carboplatin and gefitinib (Iressa, ZD1839) as first-line chemotherapy in patients with advanced breast cancer: a phase II study. 26th San Antonio Breast Cancer Symposium 2003; Abstract357.

    Google Scholar 

  159. Robertson JFR, Gutteridge E, Cheung KL, etal. Gefitinib (ZD1839) is active in acquired tamoxifen (TAM)-resistant oestrogen receptor (ER)-positive and ER-negative breast cancer: results from a phase II study. Proc Am Soc Clin Oncol 2003; 22, Abstract23.

    Google Scholar 

  160. Giaccone G, Johnson DH, Manegold C. A phase III clinical trial of ZD1839 (“Iressa”) in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced non-small cell lung cancer (INTACT 1. Ann Oncol 2002; 13, Abstract40.

    Google Scholar 

  161. Johnson DH, Herbst RS, Giaccone G. ZD1839 (“Iressa”) in combination with paclitaxel and carboplatin in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC): results from a phase III clinical trial (INTACT 2). Ann Oncol 2002; 13, Abstract4680.

    Google Scholar 

  162. Dancey JE, Freidlin B. Targeting epidermal growth factor receptor–are we missing the mark? Lancet 2003; 362,62–64.

    PubMed  CAS  Google Scholar 

  163. Lynch TJ, Bell DW, Sordella R, etal. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350, 2129–2139.

    PubMed  CAS  Google Scholar 

  164. Paez JG, Janne PA, Lee JC, etal. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304, 1497–1500.

    PubMed  CAS  Google Scholar 

  165. Akita RW, Sliwkowski MX. Preclinical studies with Erlotinib (Tarceva). Semin Oncol 2003; 30,15–24.

    PubMed  CAS  Google Scholar 

  166. Iwata KK, Provoncha K, Gibson N. Inhibition of mutant EGFRvIII transformed cells by tyrosine kinase inhibitor OSI-774 (Tarceva). Proc Am Soc Clin Oncol 2002; 21, Abstract79.

    Google Scholar 

  167. Gatzemeier U, Pluzanska A, Szczesna A. Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2004; 23, Abstract7010.

    Google Scholar 

  168. Herbst RS, Prager D, Hermann R. TRIBUTE– a phase III trial of erlotinib HCl (OSI-774) combined with carboplatin and paclitaxel (CP) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2004; 23, Abstract7011.

    Google Scholar 

  169. Ritter CA, Arteaga CL. The epidermal growth factor receptor-tyrosine kinase: a promising therapeutic target in solid tumors. Semin Oncol 2003; 30,3–11.

    PubMed  CAS  Google Scholar 

  170. Harari PM, Huang S, Herbst RS, Quon H. Molecular Targeting of the Epidermal Growth Factor Receptor in Head and Neck Cancer. Lippincott, Williams and Wilkins, 2003.

    Google Scholar 

  171. Harari PM, Huang SM. Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Semin Radiat Oncol 2001; 11, 281–289.

    PubMed  CAS  Google Scholar 

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Authors
  1. Gregory W. Allen MD, PhD
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  2. Paul M. Harari MD
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Editors and Affiliations

  1. Department of Pharmacology and Toxicology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA

    David A. Gewirtz

  2. Departments of Medicine, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Shawn E. Holt

  3. Departments of Pathology, Human Genetics, Pharmacology and Toxicology, Biochemistry and Massey Cancer Center, Virginia Commonwealth, Richmond, VA

    Steven Grant

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Allen, G.W., Harari, P.M. (2007). The Advancement of Epidermal Growth Factor Receptor Inhibitors in Cancer Therapy. In: Gewirtz, D.A., Holt, S.E., Grant, S. (eds) Apoptosis, Senescence, and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-221-2_18

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  • DOI: https://doi.org/10.1007/978-1-59745-221-2_18

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