EGF Receptor in Tumor Growth and Progression (Ernst Schering Foundation Symposium Proceedings, 19)

Members of the tyrosine kinase family are frequently implicated in experimental as well as in human cancer. The best studied receptor signaling system from this family is the EGF receptor. Experts in this area report on the involvement of the receptor in a variety of human tumors, outline underlying molecular mechanisms for aberrant receptor signaling in experimental systems and present the status of current therapies directed against the receptor. A detailed analysis of EGF receptor signal transduction via expression of receptor, ligands, phosphatases and presence of other members of the receptor family will provide new information for the design of therapeutic modalities targeting this receptor system. Front Matter....Pages I-XIV Signal Transduction by EGF Receptor Tyrosine Kinase....Pages 1-17 Characterization of Growth Factor Receptor-Directed Protein Tyrosine Phosphatases....Pages 19-44 Interaction of Heparin-Binding EGF-Like Growth Factor with Multiple Receptors....Pages 45-64 Epidermal Growth Factor Receptor Expression in Head and Neck Tumorigenesis and Saturation of EGFR with Monoclonal Antibody RG83852....Pages 65-87 EGF Receptors as a Target for Therapy and Interactions with Angiogenesis....Pages 89-103 erbB Signalling and Endocrine Sensitivity of Human Breast Cancer....Pages 105-128 The Role of Estrogen in the Regulation of EGFR Expression....Pages 129-154 Multifunctional Growth Factors in Tumor Progression....Pages 155-164 The Role of Epidermal Growth Factor Receptor in the Initiation and Progression of Malignancy....Pages 165-183 Preclinical Studies with Human Tumour Xenografts Using Rat Monoclonal Antibodies Directed Against the Epidermal Growth Factor Receptor....Pages 185-209 Recombinant Fusion Toxins Targeted to Members of the ErbB Family of Receptor Tyrosine Kinases....Pages 211-232 EGF Receptor Inhibition by Antibody as Anticancer Therapy....Pages 233-251 Back Matter....Pages 253-258 The last 15 years have brought an understanding of growth and differentiation at the molecular level, expanding our knowledge of the origin and progression of cancer. Early breakthroughs defining growth control pathways came via studies of oncogenes, mutated signaling molecules that have lost the capacity to tum off their proliferative signal. Oncogenes with diverse growth-promoting activities have been discovered, covering the gamut from cell surface to nuclear signaling. Sequencing of these oncogenes revealed that they were mutated forms of captured cellular genes and displayed tyrosine kinase activity. The epidermal growth factor (EGF) receptor was the first of 40-50 transmembrane tyrosine kinase receptors to be cloned and sequenced. Beyond cell proliferation, activation of EGF receptor by its specific ligands controls important physiological processes, such as cell differentiation, apoptosis, cell migration, and cell shape. Activation of autocrine growth loops, consisting in solid human tumors of upregulated expression of EGFR together with increased production of ligands suggested its crucial role in autonomous tumor growth.