The epidermal growth factor receptor and its inhibition in cancer therapy.

Much effort has been expended in the search for inhibitors of signalling molecules that may prove to be important therapeutically in cancer. The epidermal growth factor receptor (EGFR) family and their associated ligands has been one such area extensively investigated. The complex nature of EGFR biology allows for potential opportunities for EGFR inhibitors in a number of areas of cancer therapy, including proliferative, angiogenic, invasive, and metastatic aspects. Much positive evidence of likely benefit has already been gathered from a multiplicity of laboratory experiments. Clinical trials are now urgently required to further evaluate the advantages of such agents.

[1]  G. Powis Signalling pathways as target for anticancer drug development , 1994 .

[2]  A. Levitzki Targeting signal transduction for disease therapy , 1997, Medical oncology.

[3]  D. Tindall,et al.  Epidermal growth factor induces cyclin D1 in a human prostate cancer cell line , 1998, The Prostate.

[4]  Y. Nio,et al.  Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. , 1997, Anticancer research.

[5]  N. Haites,et al.  Epidermal growth factor (EGF) increases the in vitro invasion, motility and adhesion interactions of the primary renal carcinoma cell line, A704. , 1996, European journal of cancer.

[6]  K. Gibson,et al.  Epidermal growth factor receptor tyrosine kinase: Structure-activity relationships and antitumour activity of novel quinazolines , 1997 .

[7]  Y. Kuratomi,et al.  Thioridazine enhances lysosomal accumulation of epidermal growth factor and toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin. , 1986, Experimental cell research.

[8]  D. Davies,et al.  Targeting the epidermal growth factor receptor for therapy of carcinomas. , 1996, Biochemical pharmacology.

[9]  A. Klippel,et al.  Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt , 1997, Molecular and cellular biology.

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

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

[12]  T. Beckers,et al.  Overexpression of EGFR and c‐erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts , 1998, FEBS letters.

[13]  R. Kannagi,et al.  Alteration of integrins by heparin-binding EGF-like growth factor in human breast cancer cells. , 1996, Oncology.

[14]  A. Wells,et al.  In vitro invasiveness of DU-145 human prostate carcinoma cells is modulated by EGF receptor-mediated signals , 1995, Clinical & Experimental Metastasis.

[15]  J. Arends,et al.  CD44v6 is not a prognostic factor in primary breast cancer. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[16]  P. Low,et al.  Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  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.

[18]  S. Takashima,et al.  Association of epidermal growth factor-related peptides and type I receptor tyrosine kinase receptors with prognosis of human colorectal carcinomas. , 1995, Japanese journal of clinical oncology.

[19]  J. Mendelsohn,et al.  Epidermal growth factor receptor family and chemosensitization. , 1997, Journal of the National Cancer Institute.

[20]  C. Bucana,et al.  Preferential Activation of the Epidermal Growth Factor Receptor in Human Colon Carcinoma Liver Metastases in Nude Mice , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[21]  P. Liberski,et al.  Differential activation of total and EGF receptor (EGF-R) tyrosine kinase (tyr-k) in the rectal mucosa in patients with adenomatous polyps, ulcerative colitis and colon cancer. , 1997, Hepato-gastroenterology.

[22]  N. Shimizu,et al.  Suppression of an epidermal growth factor receptor-hyperproducing tumor by an immunotoxin conjugate of gelonin and a monoclonal anti-epidermal growth factor receptor antibody. , 1989, Cancer research.

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

[24]  Alexander Levitzki,et al.  Signal-transduction therapy , 1994 .

[25]  E. Haber,et al.  Vascular Endothelial Growth Factor Induces Heparin-binding Epidermal Growth Factor-like Growth Factor in Vascular Endothelial Cells* , 1998, The Journal of Biological Chemistry.

[26]  D. Lawrence,et al.  Protein kinase inhibitors: the tyrosine-specific protein kinases. , 1998, Pharmacology & therapeutics.

[27]  A. Levitzki,et al.  Tyrosine kinase inhibition: an approach to drug development. , 1995, Science.

[28]  M. Salgaller American Association for Cancer Research , 2000, Expert opinion on investigational drugs.

[29]  I. Pastan,et al.  Adenovirus-induced release of epidermal growth factor and pseudomonas toxin into the cytosol of KB cells during receptor-mediated endocytosis , 1983, Cell.

[30]  H. Sasano,et al.  Expression of Epidermal Growth Factor‐Related Proteins and Epidermal Growth Factor Receptor in Common Epithelial Ovarian Tumors , 1997, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[31]  G. Gores,et al.  Inhibition of epidermal growth factor receptor kinase induces protease-dependent apoptosis in human colon cancer cells. , 1998, Gastroenterology.

[32]  A. Giordano,et al.  Cell cycle: Molecular targets for diagnosis and therapy: Tumor suppressor genes and cell cycle progression in cancer , 1998, Journal of cellular biochemistry.

[33]  J G Klijn,et al.  The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. , 1992, Endocrine reviews.

[34]  D. Shugar Protein kinase inhibitors--potential chemotherapeutic agents. , 1995, Acta biochimica Polonica.

[35]  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.

[36]  E. Bongcam-Rudloff,et al.  Cell scattering and migration induced by autocrine transforming growth factor alpha in human glioma cells in vitro. , 1997, Cancer research.

[37]  American Association for Cancer Research 1997: progress and new hope in the fight against cancer. , 1997, Expert opinion on investigational drugs.

[38]  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.

[39]  D. Ruiter,et al.  The role of vascular permeability factor and basic fibroblast growth factor in tumor angiogenesis. , 1995, Biological chemistry Hoppe-Seyler.

[40]  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.

[41]  P. Sismondi,et al.  The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. , 1996, British Journal of Cancer.

[42]  V. Abeler,et al.  Evaluation of the prognostic significance of cathepsin D, epidermal growth factor receptor, and c‐erbB‐2 in early cervical squamous cell carcinoma: An immunohistochemical study , 1996, Cancer.

[43]  W. Denny,et al.  Inhibition of growth of primary human tumour cell cultures by a 4-anilinoquinazoline inhibitor of the epidermal growth factor receptor family of tyrosine kinases. , 1998, European journal of cancer.

[44]  M Hosokawa,et al.  Enhancing effects of epidermal growth factor on human squamous cell carcinoma motility and matrix degradation but not growth. , 1996, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[45]  A. Bridges,et al.  Editorial Oncologic, Endocrine & Metabolic: The current status of tyrosine kinase inhibitors: Do the diarylamine inhibitors of the EGF receptor represent a new beginning? , 1995 .

[46]  D. W. Fry,et al.  Inhibitors of tyrosine kinase , 1997, Current opinion in oncology.

[47]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[48]  S. Rabbani,et al.  Role of urokinase (uPA) and its receptor (uPAR) in invasion and metastasis of hormone-dependent malignancies. , 1998, International journal of oncology.

[49]  M. Beckmann,et al.  Expression analyses of epidermal growth factor receptor and HER-2/neu: no advantage of prediction of recurrence or survival in breast cancer patients. , 1996, Oncology.

[50]  K. Gibson,et al.  ZD1839, AN EPIDERMAL GROWTH FACTOR TYROSINE KINASE INHIBITOR SELECTED FOR CLINICAL DEVELOPMENT , 1997 .

[51]  L. Norton,et al.  The Epidermal Growth Factor Receptor Modulates the Interaction of E-cadherin with the Actin Cytoskeleton* , 1998, The Journal of Biological Chemistry.

[52]  R. Fridman,et al.  Epidermal growth factor and amphiregulin up‐regulate matrix metalloproteinase‐9 (MMP‐9) in human breast cancer cells , 1997, International journal of cancer.

[53]  L. Pustilnik,et al.  Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. , 1997, Cancer research.

[54]  P. Kolm,et al.  Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation. , 1996, International journal of radiation oncology, biology, physics.

[55]  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.

[56]  D. Neal,et al.  Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor. , 1996, British Journal of Cancer.

[57]  A. Ruíz,et al.  Prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) in primary breast cancer and their relation to estradiol receptor (ER) status. , 1997, Clinica chimica acta; international journal of clinical chemistry.

[58]  H. Modjtahedi,et al.  Significance of the c-erbB family of receptor tyrosine kinases in metastatic cancer and their potential as targets for immunotherapy. , 1994, Invasion & metastasis.

[59]  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.

[60]  Kazuhiro Yoshida,et al.  Expression of several growth factors and their receptor genes in human colon carcinomas , 1990, Virchows Archiv. B, Cell pathology including molecular pathology.

[61]  H. Dvorak,et al.  Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. , 1995, The American journal of pathology.

[62]  R. Taetle,et al.  Effects of anti-epidermal growth factor (EGF) receptor antibodies and an anti-EGF receptor recombinant-ricin A chain immunoconjugate on growth of human cells. , 1988, Journal of the National Cancer Institute.

[63]  D. Davies,et al.  Epidermal growth factor receptor tyrosine kinase. Investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor. , 1994, Biochemical pharmacology.

[64]  S. Barsky,et al.  Genistein inhibits both constitutive and EGF-stimulated invasion in ER-negative human breast carcinoma cell lines. , 1998, Anticancer research.

[65]  G. Tortora,et al.  Interactions between the epidermal growth factor receptor and type I protein kinase A: biological significance and therapeutic implications. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[66]  F. Russo,et al.  EGF, TGF-a, and EGF-R in Human Colorectal Adenocarcinoma , 1998 .

[67]  Atsushi Ochiai,et al.  Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma , 1988, International journal of cancer.

[68]  H. Kato,et al.  A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. , 1996, European journal of cancer.

[69]  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.

[70]  J. Grandis,et al.  Downmodulation of TGF‐α protein expression with antisense oligonucleotides inhibits proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells , 1998, Journal of cellular biochemistry.

[71]  A. Vecchione,et al.  EGF-R expression in ductal breast cancer: proliferation and prognostic implications. , 1997, Anticancer research.

[72]  R. Khokha,et al.  Matrix metalloproteinases and tissue inhibitor of metalloproteinases: a review of their role in tumorigenesis and tissue invasion. , 1989, Invasion & metastasis.

[73]  M. Hung,et al.  Mitosis-specific Negative Regulation of Epidermal Growth Factor Receptor, Triggered by a Decrease in Ligand Binding and Dimerization, Can Be Overcome by Overexpression of Receptor* , 1997, The Journal of Biological Chemistry.

[74]  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.

[75]  R. Derynck,et al.  Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. , 1986, Science.

[76]  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.

[77]  N. Normanno,et al.  Epidermal growth factor-related peptides as targets for experimental therapy of human colon carcinoma. , 1998, Cancer detection and prevention.

[78]  H. Takamura,et al.  Interrelationship between transforming growth factor-alpha and epidermal growth factor receptor in advanced gastric cancer. , 1992, Oncology.

[79]  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.

[80]  I. Pastan,et al.  Verapamil enhances the toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin and antitransferrin receptor with pseudomonas exotoxin , 1984, Journal of Cellular Physiology.

[81]  P. Wersäll,et al.  Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma , 1997, Cancer Immunology, Immunotherapy.

[82]  J. Lunec,et al.  Matrix metalloproteinase-1 is induced by epidermal growth factor in human bladder tumour cell lines and is detectable in urine of patients with bladder tumours. , 1998, British Journal of Cancer.

[83]  D. Schuppan,et al.  Prevention of EGF‐modulated adhesion of tumor cells to matrix proteins by specific EGF receptor inhibition , 1998, International journal of cancer.

[84]  R. Lavker,et al.  EGF-R dependent regulation of keratinocyte survival. , 1997, Journal of cell science.

[85]  H. Bier,et al.  Antitumor activity of anti-epidermal growth factor receptor monoclonal antibodies and cisplatin in ten human head and neck squamous cell carcinoma lines. , 1997, Anticancer research.

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

[87]  K. Fujikawa,et al.  The Ets‐1 and Ets‐2 transcription factors activate the promoters for invasion‐associated urokinase and collagenase genes in response to epidermal growth factor , 1998, International journal of cancer.

[88]  A. Wells,et al.  Cell movement elicited by epidermal growth factor receptor requires kinase and autophosphorylation but is separable from mitogenesis , 1994, The Journal of cell biology.

[89]  C. Bucana,et al.  Expression of metastasis-related genes in surgical specimens of human gastric cancer can predict disease recurrence , 1998 .

[90]  A. Lage,et al.  A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: report of a pilot clinical trial. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[91]  G. Kouraklis,et al.  Increased estrogen receptor and epidermal growth factor receptor gene product co‐expression in surgically resected gastric adenocarcinomas , 1996, Journal of surgical oncology.

[92]  S. Ranga,et al.  Comparative evaluation of cell proliferative indices and epidermal growth factor receptor expression in gastric carcinoma. , 1997, Indian journal of pathology & microbiology.

[93]  G. Fontanini,et al.  Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A. , 1996, Journal of the National Cancer Institute.

[94]  G. Niehans,et al.  Immunohistochemical staining for markers of future neoplastic progression in the larynx. , 1996, Cancer research.

[95]  W. Evans,et al.  In vivo toxicity, pharmacokinetics, and anticancer activity of Genistein linked to recombinant human epidermal growth factor. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[96]  Peter Traxler,et al.  Protein tyrosine kinase inhibitors in cancer treatment , 1997 .

[97]  R. Dickson,et al.  The EGF receptor system as a target for antitumor therapy. , 1991, Cancer investigation.

[98]  R. Cozens,et al.  A potent protein‐tyrosine kinase inhibitor which selectively blocks proliferation of epidermal growth factor receptor‐expressing tumor cells in vitro and in vivo , 1998 .

[99]  Gary R. Grotendorst,et al.  EGF and TGF‐alpha are potent chemoattractants for endothelial cells and EGF‐like peptides are present at sites of tissue regeneration , 1989, Journal of cellular physiology.

[100]  F. Uckun,et al.  Cytotoxic activity of epidermal growth factor-genistein against breast cancer cells. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[101]  C. Angeletti,et al.  Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[102]  A. Akdaş,et al.  Impact of the expression of epidermal growth factor, transforming growth factor alpha, and epidermal growth factor receptor on the prognosis of superficial bladder cancer. , 1998, Urology.

[103]  M. Volm,et al.  Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. , 1998, British Journal of Cancer.

[104]  L. Matrisian,et al.  Changing views of the role of matrix metalloproteinases in metastasis. , 1997, Journal of the National Cancer Institute.

[105]  A. Vollmar,et al.  Toxicity of ligand and antibody‐directed ricin A‐chain conjugates recognizing the epidermal growth factor receptor , 1987, Journal of cellular physiology.

[106]  Robert S. Kerbel,et al.  Establishing a Link between Oncogenes and Tumor Angiogenesis , 1998, Molecular medicine.

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

[108]  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.

[109]  R. Swerlick,et al.  Transforming growth factor‐α‐induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP‐2‐dependent DNA binding and transactivation , 1997, The EMBO journal.