Epidermal growth factor receptor biology (IMC-C225)

Treatment of solid tumors despite improved techniques in detection, surgery, radiation therapy, and chemotherapy remains difficult. Therefore, strategies to improve efficacy in accord with safety are needed. Many epithelial cancers have been found to overexpress the receptor to epidermal growth factor (EGFR), including head and neck, breast, colon, lung, prostate, kidney, ovary, brain, pancreas, and bladder. Because overexpression of EGFR has been associated with an overall poor prognosis in patients with cancer, a number of strategies to block or downregulate EGFR have been developed to inhibit tumor proliferation and improve overall clinical outcome. These include monoclonal antibodies to the EGFR, tyrosine kinase inhibitors, ligand-linked toxins, and antisense approaches. Antibodies such as IMC-C225 specifically target EGF receptors, whereas tyrosine kinase inhibition by many small molecules is less specific. Ultimately, IMC-C225 may prove to become a valuable contributor in the treatment of cancer. This report will focus on IMC-C225, a novel monoclonal antibody that targets the EGFR.

[1]  R. Day,et al.  Levels of TGF-α and EGFR Protein in Head and Neck Squamous Cell Carcinoma and Patient Survival , 1998 .

[2]  H. Sasano,et al.  Epidermal growth factor receptor overexpression in esophageal carcinoma. An immunohistochemical study correlated with clinicopathologic findings and DNA amplification , 1994, Cancer.

[3]  Roy S Herbst,et al.  Monoclonal antibodies to target epidermal growth factor receptor–positive tumors , 2002, Cancer.

[4]  G. Carpenter,et al.  Receptors for epidermal growth factor and other polypeptide mitogens. , 1987, Annual review of biochemistry.

[5]  L. Norton,et al.  Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  R H Wheeler,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. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  N. Normanno,et al.  Epidermal growth factor-related peptides and their receptors in human malignancies. , 1995, Critical reviews in oncology/hematology.

[8]  W. Hong,et al.  Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. , 1994, Cancer research.

[9]  A. Yung,et al.  Differential expression of epidermal growth factor receptor in human head and neck cancers , 1998, Head & neck.

[10]  T. Yamamoto,et al.  Gene amplification and overexpression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck , 1992, Head & neck.

[11]  W. Gullick,et al.  Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers. , 1991, British medical bulletin.

[12]  D. Hicklin,et al.  Epidermal growth factor receptor blockade by antibody IMC‐C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice , 2000, Cancer.

[13]  P. Harari,et al.  Modulation of molecular targets to enhance radiation. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  D. Bigner,et al.  Prognostic applications of the epidermal growth factor receptor and its ligand, transforming growth factor-alpha. , 1998, Journal of the National Cancer Institute.

[15]  G. Tortora,et al.  Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  N. Goldstein,et al.  Anti-tumor and cell cycle responses in KB cells treated with a chimeric anti-EGFR monoclonal antibody in combination with cisplatin. , 1996, International journal of oncology.

[17]  C. Dinney,et al.  Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  J. Schlessinger The epidermal growth factor receptor as a multifunctional allosteric protein. , 1988, Biochemistry.

[19]  G. Gill,et al.  The EGF receptor: structure, regulation and potential role in malignancy. , 1985, Cancer surveys.

[20]  J. Ghrayeb,et al.  Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C. Sartor,et al.  Biological modifiers as potential radiosensitizers: targeting the epidermal growth factor receptor family. , 2000, Seminars in oncology.

[22]  O. Bogler,et al.  A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. , 1996, Cancer research.

[23]  A. Belldegrun,et al.  Epidermal growth factor receptor gene expression in normal human kidney and renal cell carcinoma. , 1989, The Journal of urology.

[24]  G. Paludetti,et al.  Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. , 1996, British Journal of Cancer.

[25]  N. Goldstein,et al.  Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. , 1997, The American journal of pathology.

[26]  H. Modjtahedi,et al.  EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5. , 1998, International journal of oncology.

[27]  P. Harari,et al.  Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[28]  G. Gibson,et al.  The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. , 1993, British Journal of Cancer.

[29]  H. Tideman Quantitative immunohistochemical analysis of transforming growth factor-α and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck , 1999 .

[30]  M. Rubin,et al.  Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody. , 1996, Oncogene.

[31]  P. Harari,et al.  Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. , 1999, Cancer research.

[32]  N. Goldstein,et al.  Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  N. Rosen,et al.  Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. , 1995, The Journal of clinical investigation.

[34]  N. Goldstein,et al.  The biologic effects of C225, a chimeric monoclonal antibody to the EGFR, on human prostate carcinoma. , 1996, Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy.

[35]  H. Fox,et al.  Prognostic value of epidermal growth factor receptor expression in cervical carcinoma. , 1993, Journal of clinical pathology.

[36]  S. Maeda,et al.  Amplification and overexpression of the epidermal growth factor receptor gene in human renal‐cell carcinoma , 1990, International journal of cancer.

[37]  H. Scher,et al.  Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145. , 1996, Cancer research.

[38]  J. Mendelsohn,et al.  Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in DiFi human colon cancer cells do not involve the c- jun N-terminal kinase activity , 2000, British Journal of Cancer.

[39]  K. Ang,et al.  In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[40]  T. Cooke,et al.  Quantitative estimation of epidermal growth factor receptor and c-erbB-2 in human breast cancer. , 1996, Cancer research.

[41]  W. Grizzle,et al.  Combined modality therapy of A431 human epidermoid cancer using anti-EGFr antibody C225 and radiation. , 1999, Cancer biotherapy & radiopharmaceuticals.

[42]  D B Evans,et al.  Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[43]  J. Mendelsohn Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[44]  C. Bucana,et al.  Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[45]  T. Tzai,et al.  Significance of urinary epidermal growth factor and its receptor expression in human bladder cancer. , 1997, Anticancer research.

[46]  J. Baselga,et al.  Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. , 1993, Cancer research.

[47]  J. W. Lee,et al.  Expression of epidermal growth factor receptor in carcinoma of the cervix. , 1996, Gynecologic oncology.

[48]  M. Mandal,et al.  Nuclear targeting of Bax during apoptosis in human colorectal cancer cells , 1998, Oncogene.

[49]  S. Cohen,et al.  Epidermal growth factor , 1972, The Journal of investigative dermatology.

[50]  A. Ullrich,et al.  Growth factor receptor tyrosine kinases. , 1988, Annual review of biochemistry.

[51]  R. Bast,et al.  Cell growth regulation in epithelial ovarian cancer , 1993, Cancer.

[52]  H. Heinzl,et al.  EGFR and steroid receptors in ovarian carcinoma: comparison with prognostic parameters and outcome of patients. , 1997, Anticancer research.

[53]  M. Droller Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. , 2000, The Journal of urology.

[54]  J. Grandis,et al.  Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. , 1998, Journal of the National Cancer Institute.

[55]  R. Day,et al.  Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. , 1998, Journal of the National Cancer Institute.

[56]  P. V. van Diest,et al.  Expression of growth factors, growth‐inhibiting factors, and their receptors in invasive breast cancer. II: Correlations with proliferation and angiogenesis , 1998, The Journal of pathology.

[57]  P. Harari,et al.  Head and neck cancer as a clinical model for molecular targeting of therapy: combining EGFR blockade with radiation. , 2001, International journal of radiation oncology, biology, physics.

[58]  L. Norton,et al.  Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. , 1993, Journal of the National Cancer Institute.