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The role of epidermal growth factor receptor in head and neck squamous cell carcinoma

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Abstract

Growth factor receptors play a crucial role in the cell proliferation pathways involved in the development of cancer. One such receptor, the epidermal growth factor receptor (EGFR), is upregulated in many types of human tumors, particularly head and neck squamous cell carcinoma (HNSCC). EGFR overexpression in HNSCC has been the basis for investigation of therapeutic strategies that target EGFR. EGFR-blocking methods under evaluation involve immunotoxins, monoclonal antibodies, EGFR-specific tyrosine kinase inhibitors, and antisense approaches. These molecular targeting tactics have produced a number of agents that are currently in various stages of preclinical investigation, along with clinical trials to assess their potential as anticancer treatments.

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References and Recommended Reading

  1. Rubin Grandis J, Tweardy DJ: Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993, 53:3579–3584.

    Google Scholar 

  2. Rubin Grandis J, Melhem MF, Barnes EL, et al.: Quantitative immunohistochemical analysis of transforming growth factor-alpha and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck. Cancer 1996, 78:1284–1292.

    Article  PubMed  CAS  Google Scholar 

  3. Ke LD, Adler-Storthz K, Clayman GL, et al.: Differential expression of epidermal growth factor receptor in human head and neck cancers. Head Neck 1998, 20:320–327.

    Article  PubMed  CAS  Google Scholar 

  4. Johannessen LE, Haugen KE, Ostvold AC, et al.: Heterodimerization of the epidermal-growth-factor (EGF) receptor and ErbB2 and the affinity of EGF binding are regulated by different mechanisms. Biochem J 2001, 356:87–96.

    Article  PubMed  CAS  Google Scholar 

  5. Fernandes AM, Hamburger AW, Gerwin BI: Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity. Am J Respir Cell Mol Biol 1999, 21:701–709.

    PubMed  CAS  Google Scholar 

  6. Brandt BH, Roetger A, Dittmar T, et al.: c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells. FASEB J 1999, 13:1939–1949.

    PubMed  CAS  Google Scholar 

  7. Noguchi H, Sakamoto C, Wada K, et al.: Expression of heregulin alpha, erbB2, and erbB3 and their influences on proliferation of gastric epithelial cells. Gastroenterology 1999, 117:1119–1127.

    Article  PubMed  CAS  Google Scholar 

  8. Earp HS, Dawson TL, Li X, et al.: Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat 1995, 35:115–132.

    Article  PubMed  CAS  Google Scholar 

  9. Slichenmyer WJ, Fry DW: Anticancer therapy targeting the erbB family of receptor tyrosine kinases. Semin Oncol 2001, 28(Suppl 16):67–79.

    Article  PubMed  CAS  Google Scholar 

  10. Field JK, Spandidos DA, Yiagnisis M, et al.: C-erbB-2 expression in squamous cell carcinoma of the head and neck. Anticancer Res 1992, 12:613–619.

    PubMed  CAS  Google Scholar 

  11. Craven JM, Pavelic ZP, Stambrook PJ, et al.: Expression of c-erbB-2 gene in human head and neck carcinoma. Anticancer Res 1992, 12:2273–2276.

    PubMed  CAS  Google Scholar 

  12. Khan AJ, King BL, Smith BD, et al.: Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma. Clin Cancer Res 2002, 8:540–548.

    PubMed  CAS  Google Scholar 

  13. Xia W, Lau YK, Zhang HZ, et al.: Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res 1999, 5:4164–4174.

    PubMed  CAS  Google Scholar 

  14. Wallasch C, Weiss FU, Niederfellner G, et al.: Heregulindependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. Embo J 1995, 14:4267–4275.

    PubMed  CAS  Google Scholar 

  15. Shintani S, Funayama T, Yoshihama Y, et al.: Prognostic significance of ERBB3 overexpression in oral squamous cell carcinoma. Cancer Lett 1995, 95:79–83.

    Article  PubMed  CAS  Google Scholar 

  16. Bei R, Pompa G, Vitolo D, et al.: Co-localization of multiple ErbB receptors in stratified epithelium of oral squamous cell carcinoma. J Pathol 2001, 195:343–348.

    Article  PubMed  CAS  Google Scholar 

  17. Ibrahim SO, Vasstrand EN, Liavaag PG, et al.: Expression of c-erbB proto-oncogene family members in squamous cell carcinoma of the head and neck. Anticancer Res 1997, 17:4539–4546.

    PubMed  CAS  Google Scholar 

  18. Fujino S, Enokibori T, Tezuka N, et al.: A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur J Cancer 1996, 32A:2070–2074.

    Article  PubMed  CAS  Google Scholar 

  19. Ohsaki Y, Tanno S, Fujita Y, et al.: Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep 2000, 7:603–607.

    PubMed  CAS  Google Scholar 

  20. Rajkumar T, Gullick WJ: The type I growth factor receptors in human breast cancer. Breast Cancer Res Treat 1994, 29:3–9.

    Article  PubMed  CAS  Google Scholar 

  21. Bucci B, D’Agnano I, Botti C, et al.: EGF-R expression in ductal breast cancer: proliferation and prognostic implications. Anticancer Res 1997, 17:769–774.

    PubMed  CAS  Google Scholar 

  22. de Jong JS, van Diest PJ, van der Valk P, et al.: Expression of growth factors, growth factor receptors and apoptosis related proteins in invasive breast cancer: relation to apoptotic rate. Breast Cancer Res Treat 2001, 66:201–208.

    Article  PubMed  Google Scholar 

  23. Cohen DW, Simak R, Fair WR, et al.: Expression of transforming growth factor-alpha and the epidermal growth factor receptor in human prostate tissues. J Urol 1994, 152:2120–2124.

    PubMed  CAS  Google Scholar 

  24. Schwartz S Jr, Caceres C, Morote J, et al.: Gains of the relative genomic content of erbB-1 and erbB-2 in prostate carcinoma and their association with metastasis. Int J Oncol 1999, 14:367–371.

    PubMed  CAS  Google Scholar 

  25. Chow NH, Liu HS, Lee EI, et al.: Significance of urinary epidermal growth factor and its receptor expression in human bladder cancer. Anticancer Res 1997, 17:1293–1296.

    PubMed  CAS  Google Scholar 

  26. Cardillo MR, Castagna G, Memeo L, et al.: Epidermal growth factor receptor, MUC-1 and MUC-2 in bladder cancer. J Exp Clin Cancer Res 2000, 19:225–233.

    PubMed  CAS  Google Scholar 

  27. Nouri AM, Cannell H, Dagini B, et al.: Profile of p53 expression in bladder and oral tumours: effects of in vitro manipulations of p53 on the behaviour of established human tumour cell lines. Eur J Cancer 2000, 36:1853–1862.

    Article  PubMed  CAS  Google Scholar 

  28. Kirby RE, Lewandrowski KB, Southern JF, et al.: Relation of epidermal growth factor receptor and estrogen receptorindependent pS2 protein to the malignant transformation of mucinous cystic neoplasms of the pancreas. Arch Surg 1995, 130:69–72.

    PubMed  CAS  Google Scholar 

  29. Uegaki K, Nio Y, Inoue Y, et al.: Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. Anticancer Res 1997, 17:3841–3847.

    PubMed  CAS  Google Scholar 

  30. Friess H, Wang L, Zhu Z, et al.: Growth factor receptors are differentially expressed in cancers of the papilla of vater and pancreas. Ann Surg 1999, 230:767–775.

    Article  PubMed  CAS  Google Scholar 

  31. Ekstrand AJ, James CD, Cavenee WK, et al.: Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 1991, 51:2164–2172.

    PubMed  CAS  Google Scholar 

  32. Kordek R, Bratosiewicz J, Biernat W, et al.: Expression of p53-protein, epidermal growth factor receptor (EGFR) and proliferating cell antigens in human gliomas. Folia Neuropathol 1994, 32:227–228.

    PubMed  CAS  Google Scholar 

  33. Wang XY, Smith DI, Frederick L, et al.: Analysis of EGF receptor amplicons reveals amplification of multiple expressed sequences. Oncogene 1998, 16:191–195.

    Article  PubMed  CAS  Google Scholar 

  34. Ishikawa J, Maeda S, Umezu K, et al.: Amplification and overexpression of the epidermal growth factor receptor gene in human renal-cell carcinoma. Int J Cancer 1990, 45:1018–1021.

    Article  PubMed  CAS  Google Scholar 

  35. Untawale S, Zorbas MA, Hodgson CP, et al.: Transforming growth factor-alpha production and autoinduction in a colorectal carcinoma cell line (DiFi) with an amplified epidermal growth factor receptor gene. Cancer Res 1993, 53:1630–1636.

    PubMed  CAS  Google Scholar 

  36. Messa C, Russo F, Caruso MG, et al.: EGF, TGF-alpha, and EGF-R in human colorectal adenocarcinoma. Acta Oncol 1998, 37:285–289.

    Article  PubMed  CAS  Google Scholar 

  37. Leng J, Lang J, Shen K, et al.: Overexpression of p53, EGFR, c-erbB2 and c-erbB3 in endometrioid carcinoma of the ovary. Chin Med Sci J 1997, 12:67–70.

    PubMed  CAS  Google Scholar 

  38. Ilekis JV, Connor JP, Prins GS, et al.: Expression of epidermal growth factor and androgen receptors in ovarian cancer. Gynecol Oncol 1997, 66:250–254.

    Article  PubMed  CAS  Google Scholar 

  39. Harlozinska A, Bar JK, Sobanska E, et al.: Epidermal growth factor receptor and c-erbB-2 oncoproteins in tissue and tumor effusion cells of histopathologically different ovarian neoplasms. Tumour Biol 1998, 19:364–373.

    Article  PubMed  CAS  Google Scholar 

  40. Stanton P, Richards S, Reeves J, et al.: Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts. Br J Cancer 1994, 70:427–433.

    PubMed  CAS  Google Scholar 

  41. Santini J, Formento JL, Francoual M, et al.: Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas. Head Neck 1991, 13:132–139.

    Article  PubMed  CAS  Google Scholar 

  42. Chen BK, Ohtsuki Y, Furihata M, et al.: Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage. Int J Oncol 1999, 15:893–898.

    PubMed  CAS  Google Scholar 

  43. O-cheroenrat P, Rhys-Evans PH, Archer DJ, et al.: 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.

    Article  Google Scholar 

  44. Werkmeister R, Brandt B, Joos U: Clinical relevance of erbB-1 and -2 oncogenes in oral carcinomas. Oral Oncol 2000, 36:100–105.

    Article  PubMed  CAS  Google Scholar 

  45. Rubin Grandis J, Melhem MF, Gooding WE, et al.: 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. In this study, expression of EGFR and TGF-α was quantified in tumors excised from 91 HNSCC patients. Both EGFR and TGF-α protein levels were found to be significant predictors of disease-free and cause-specific survival.

    Article  PubMed  CAS  Google Scholar 

  46. Akslen LA, Myking AO, Salvesen H, et al.: Prognostic impact of EGF-receptor in papillary thyroid carcinoma. Br J Cancer 1993, 68:808–812.

    PubMed  CAS  Google Scholar 

  47. Chen Z, Ke LD, Yuan XH, et al.: Correlation of cisplatin sensitivity with differential alteration of EGFR expression in head and neck cancer cells. Anticancer Res 2000, 20:899–902.

    PubMed  CAS  Google Scholar 

  48. Gupta AK, McKenna WG, Weber CN, et al.: Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction. Clin Cancer Res 2002, 8:885–892.

    PubMed  Google Scholar 

  49. Pavlovskis OR, Voelker FA, Shackelford AH: Pseudomonas aeruginosa exotoxin in mice: histopathology and serum enzyme changes. J Infect Dis 1976, 133:253–259.

    PubMed  CAS  Google Scholar 

  50. Schumann J, Angermuller S, Bang R, et al.: Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF. J Immunol 1998, 161:5745–5754.

    PubMed  CAS  Google Scholar 

  51. Schumann J, Bluethmann H, Tiegs G: Synergism of Pseudomonas aeruginosa exotoxin A with endotoxin, superantigen, or TNF results in TNFR1-and TNFR2-dependent liver toxicity in mice. Immunol Lett 2000, 74:165–172.

    Article  PubMed  CAS  Google Scholar 

  52. Ilercil O, Laske DW, Walbridge S, et al.: Neurotoxicity of immunotoxins. Mol Chem Neuropathol 1994, 21:379–386.

    Article  PubMed  CAS  Google Scholar 

  53. Azemar M, Schmidt M, Arlt F, et al.: Recombinant antibody toxins specific for ErbB2 and EGF receptor inhibit the in vitro growth of human head and neck cancer cells and cause rapid tumor regression in vivo. Int J Cancer 2000, 86:269–75. Recombinant immunotoxins were formed by genetically fusing a monoclonal antibody to a Pseudomonas exotoxin. The growth of HNSCC cell lines was inhibited by two EGFR-specific toxins. One of these immunotoxins also demonstrated potent in vivo antitumor activity, leading to complete tumor regression in 50% of mice.

    Article  PubMed  CAS  Google Scholar 

  54. Seetharam S, Nodzenski E, Beckett MA, et al.: Modulation of apoptotic response of a radiation-resistant human carcinoma by Pseudomonas exotoxin-chimeric protein. Cancer Res 1998, 58:3215–3220.

    PubMed  CAS  Google Scholar 

  55. Goldberg MR, Heimbrook DC, Russo P, et al.: Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer. Clin Cancer Res 1995, 1:57–61.

    PubMed  CAS  Google Scholar 

  56. Hoffmann T, Hafner D, Ballo H, et al.: Antitumor activity of anti-epidermal growth factor receptor monoclonal antibodies and cisplatin in ten human head and neck squamous cell carcinoma lines. Anticancer Res 1997, 17:4419–4425.

    PubMed  CAS  Google Scholar 

  57. van Gog FB, Brakenhoff RH, Stigter-van Walsum M, et al.: Perspectives of combined radioimmunotherapy and anti-EGFR antibody therapy for the treatment of residual head and neck cancer. Int J Cancer 1998, 77:13–18.

    Article  PubMed  Google Scholar 

  58. Bier H, Reiffen KA, Haas I, et al.: Dose-dependent access of murine anti-epidermal growth factor receptor monoclonal antibody to tumor cells in patients with advanced laryngeal and hypopharyngeal carcinoma. Eur Arch Otorhinolaryngol 1995, 252:433–439.

    Article  PubMed  CAS  Google Scholar 

  59. Bier H, Hoffmann T, Haas I, et al.: Anti-(epidermal growth factor) receptor monoclonal antibodies for the induction of antibody-dependent cell-mediated cytotoxicity against squamous cell carcinoma lines of the head and neck. Cancer Immunol Immunother 1998, 46:167–73.

    Article  PubMed  CAS  Google Scholar 

  60. Hambek M, Solbach C, Schnuerch HG, et al.: Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor (EGFR)-expressing carcinomas for anti-EGFR therapy. Cancer Res 2001, 61:1045–1049.

    PubMed  CAS  Google Scholar 

  61. Yang XD, Jia XC, Corvalan JR, et al.: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 2001, 38:17–23.

    PubMed  CAS  Google Scholar 

  62. Harari PM, Huang SM: Head and neck cancer as a clinical model for molecular targeting of therapy: combining EGFR blockade with radiation. Int J Radiat Oncol Biol Phys 2001, 49:427–433.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  64. 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 

  65. Bonner JA, Raisch KP, Trummell HQ, et al.: Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers. J Clin Oncol 2000, 18(21 Suppl):47S-53S.

    PubMed  CAS  Google Scholar 

  66. Fan Z, Baselga J, Masui H, et al.: Antitumor effect of antiepidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 1993, 53:4637–4642.

    PubMed  CAS  Google Scholar 

  67. Robert F, Ezekiel MP, Spencer SA, et al.: Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol 2001, 19:3234–3243. In a phase I trial, C225 in conjunction with radiotherapy was tolerated well in 16 patients with advanced HNSCC. Remarkably, all patients responded to the combination treatment, with 13 (86.7%) achieving complete remission.

    PubMed  CAS  Google Scholar 

  68. Shin DM, Donato NJ, Perez-Soler R, et al.: Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 2001, 7:1204–1213. This phase I study examined the effects of C225 with the chemotherapeutic agent cisplatin on recurrent HNSCC patients with EGFR-overexpressing tumors. Therapy was generally tolerated well and in 67% of patients produced clinical responses, one third of which were complete.

    PubMed  CAS  Google Scholar 

  69. Hong WK, Arquette M, Nabell L, et al.: Efficacy and safety of the anti-epidermal growth factor antibody (EGFR) IMCC225, in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck refractory to cisplating containing chemotherapy [abstract]. Proc ASCO 2001, 20:224a.

    Google Scholar 

  70. Baselga J, Pfister D, Cooper MR, et al.: Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 2000, 18:904–914.

    PubMed  CAS  Google Scholar 

  71. Bier H, Hoffmann T, Hauser U, et al.: Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx. Cancer Chemother Pharmacol 2001, 47:519–524. The humanized antibody EMD 72000 was tolerated well when administered to advanced HNSCC patients in this phase I study. Based on these results, a weekly dose of 200 mg was deemed appropriate for future investigations of the EMD 72000 antibody.

    Article  PubMed  CAS  Google Scholar 

  72. Crombet T, Osorio M, Cruz T, et al.: Use of the anti-EGFR antibody h-R3 in combination with radiotherapy in the treatment of advanced head and neck cancer [abstract]. Proc ASCO 2002, 21:14a.

    Google Scholar 

  73. Anderson NG, Ahmad T, Chan K, et al.: ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFRpositive cancer cell lines with or without erbB2 over expression. Int J Cancer 2001, 94:774–782.

    Article  PubMed  CAS  Google Scholar 

  74. Hazaa AA, Birchall MA, Bowen ID: ZD1839 (IressaTM), an EGFR-TKI, and cisplatin have an additive effect on programmed cell death in human head and neck squamous carcinoma cells in vitro [abstract]. Proceedings of the 11th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy. Clin Cancer Res 2000, 6:4542S.

    Google Scholar 

  75. Sirotnak FM, Zakowski MF, Miller VA, et al.: 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 

  76. Ciardiello F, Caputo R, Bianco R, et al.: 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 

  77. Williams KJ, Telfer BA, Stratford IJ, et al.: 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.

    Article  PubMed  CAS  Google Scholar 

  78. Pollack VA, Savage DM, Baker DA, et al.: 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 

  79. Solorzano CC, Baker CH, Tsan R, et al.: Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma. Clin Cancer Res 2001, 7:2563–2572.

    PubMed  CAS  Google Scholar 

  80. Slichenmyer WJ, Elliott WL, Fry DW: CI-1033, a pan-erbB tyrosine kinase inhibitor. Semin Oncol 2001, 28(Suppl 16):80–85. CI-1033 is a newly developed irreversible tyrosine kinase inhibitor that is effective not only against EGFR but also against all four members of the erbB growth factor receptor family (EGFR, Her2-neu, Erb3, and Erb4). This article reviews the in vitro and in vivo preclinical studies implicating CI-1033 as a potent anticancer agent.

    Article  PubMed  CAS  Google Scholar 

  81. Zhu XF, Liu ZC, Xie BF, et al.: EGFR tyrosine kinase inhibitor AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells. Cancer Lett 2001, 169:27–32.

    Article  PubMed  CAS  Google Scholar 

  82. Sun Y, Fry DW, Vincent P, et al.: Growth inhibition of nasopharyngeal carcinoma cells by EGF receptor tyrosine kinase inhibitors. Anticancer Res 1999, 19:919–924.

    PubMed  CAS  Google Scholar 

  83. Ranson M, Hammond LA, Ferry D, et al.: ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 2002, 20:2240–2250. In this phase I study, ZD1839 was administered orally to 64 patients with solid malignant tumors. Tolerability was good, and objective clinical responses were noted in several patients.

    Article  PubMed  CAS  Google Scholar 

  84. Cohen E, Rosen F, Dekker A, et al.: Phase II study of ZD1839 (Iressa) in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proc ASCO 2002, 21:225a.

    Google Scholar 

  85. Hidalgo M, Siu LL, Nemunaitis J, et al.: Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 2001, 19:3267–3279. Forty patients with advanced solid malignancies of various origins were treated with escalating daily oral doses of OSI-774 in a phase I trial of this EGFR-specific tyrosine kinase inhibitor. The drug was tolerated well, with several partial responses observed. The results of this study suggest the feasibility of a daily oral dose of 150 mg.

    PubMed  CAS  Google Scholar 

  86. Senzer NN, Soulieres D, Siu L, et al.: Phase 2 evaluation of OSI-774, a potent oral antagonist of the EGFR-TK in patients with advanced squamous cell carcinoma of the head and neck [abstract]. Proc ASCO 2001, 20:2a.

    Google Scholar 

  87. Hoekstra R, Dumez H, van Oosterom AT, et al.: A phase I and pharmacological study of PKI166, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, administered orally in a two weeks on, two weeks off scheme to patients with advanced cancer [abstract]. Proc ASCO 2002, 21:86a.

    Google Scholar 

  88. Rubin Grandis J, Chakraborty A, Melhem MF, et al.: Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells. Oncogene 1997, 15:409–416.

    Article  PubMed  CAS  Google Scholar 

  89. Rubin Grandis J, Chakraborty A, Zeng Q, et al.: Downmodulation of TGF-alpha protein expression with antisense oligonucleotides inhibits proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells. J Cell Biochem 1998, 69:55–62.

    Article  Google Scholar 

  90. He Y, Zeng Q, Drenning SD, et al.: Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. J Natl Cancer Inst 1998, 90:1080–1087.

    Article  PubMed  CAS  Google Scholar 

  91. Endo S, Zeng Q, Burke NA, et al.: TGF-alpha antisense gene therapy inhibits head and neck squamous cell carcinoma growth in vivo. Gene Ther 2000, 7:1906–1914.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Otolaryngology, The Eye and Ear Institute, Suite 500, 200 Lothrop Street, 15213, Pittsburgh, PA, USA

    Jennifer Rubin Grandis MD

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  1. Rebecca G. Pomerantz MD
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Pomerantz, R.G., Grandis, J.R. The role of epidermal growth factor receptor in head and neck squamous cell carcinoma. Curr Oncol Rep 5, 140–146 (2003). https://doi.org/10.1007/s11912-003-0101-z

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