Epidermal growth factor receptor modulation of radiation response: preclinical and clinical development.

Approximately two thirds of all human solid tumors derive from epithelial tissues. The epidermal growth factor receptor (EGFR) serves as an important regulator of cellular growth in epithelial tumors. A spectrum of new anticancer agents have been specifically designed to target the EGFR in an effort to inhibit malignant growth. Although several of these new drugs show single-agent activity in early clinical trials, the predominant growth effect of EGFR signaling inhibition is cytostatic. However, the interaction of EGFR inhibition combined with conventional cytotoxic therapies (radiation and chemotherapy) is more potent, and shows great promise in the treatment of a variety of solid tumors that overexpress this receptor. This report focuses primarily on the capacity of EGFR inhibitors to modulate cellular and overall tumor response to ionizing radiation.

[1]  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.

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

[3]  John Mendelsohn,et al.  The EGF receptor family as targets for cancer therapy , 2000, Oncogene.

[4]  S H Kaufmann,et al.  The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. , 2001, Cancer research.

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

[6]  J. Smaill,et al.  Tyrosine kinase inhibitors. 18. 6-Substituted 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as soluble, irreversible inhibitors of the epidermal growth factor receptor. , 2001, Journal of medicinal chemistry.

[7]  A. Scott,et al.  Monoclonal antibody 806 inhibits the growth of tumor xenografts expressing either the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type EGFR. , 2001, Cancer research.

[8]  A. Ullrich,et al.  Receptor tyrosine kinase signalling as a target for cancer intervention strategies. , 2001, Endocrine-related cancer.

[9]  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.

[10]  J. Baselga.  Clinical trials of Herceptin(trastuzumab). , 2001, European journal of cancer.

[11]  J. Mendelsohn,et al.  Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. , 1983, Molecular biology & medicine.

[12]  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.

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

[14]  K. Gibson,et al.  Studies leading to the identification of ZD1839 (IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. , 2001, Bioorganic & medicinal chemistry letters.

[15]  S. Ethier,et al.  Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor. , 2000, International journal of radiation oncology, biology, physics.

[16]  W. Cavenee,et al.  Aberrant receptor signaling in human malignant gliomas: mechanisms and therapeutic implications. , 2001, Cancer Letters.

[17]  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.

[18]  G. Fontanini,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. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  P. Harari,et al.  Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. , 2001, Seminars in radiation oncology.

[20]  P. Harari,et al.  Epidermal Growth Factor Receptor Inhibition in Cancer Therapy: Biology, Rationale and Preliminary Clinical Results , 2004, Investigational New Drugs.

[21]  J. Poen,et al.  Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. , 1999, Cancer research.

[22]  J. Mendelsohn.  The epidermal growth factor receptor as a target for therapy with antireceptor monoclonal antibodies. , 1990, Seminars in cancer biology.

[23]  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.

[24]  A. Scott,et al.  Growth suppression of intracranial xenografted glioblastomas overexpressing mutant epidermal growth factor receptors by systemic administration of monoclonal antibody (mAb) 806, a novel monoclonal antibody directed to the receptor. , 2001, Cancer research.