EGFR Signaling Networks in Cancer Therapy

The epidermal growth factor (EGF) receptor and its downstream signal transduction networks have been implicated in the ontology and maintenance of tumor tissues. This volume probes and explores this fascinating system with compelling information.

The epidermal gro wth factor (EGF ) receptor and its downstream signal transduction networks have been implicated in the ontology and maintenance of tumor tissues, which has motivated the discovery and development of molecularly targeted anti-EGF receptor therapies. Over decades of study, the EGF receptor structure, its ligand binding domains, the physical biochemistry underlying its intrinsic tyrosine kinase catalytic function and the modular interactions with SH2, PTB, and SH3 domain containing signaling adaptor p- teins required for signal transduction, have been extensively dissected. Not only is the EGF receptor the nexus of many streams of information, but it also forms one part of a calcul- ing device by forming dimers and oligomers with the other three receptors in its family in response to at least eleven ligands (some of which are expressed in multiple forms with overlapping or quite distinct functions). This phenomenon, while recruiting to the inner surface of the cell membrane and activating multiple second messenger proteins, also allows the possibility of cross talk between these systems, permitting a further layer of information to be exchanged. Less well described are the cross re gulation of the EGF receptor and other anti-apoptotic, mitogenic and metabolic signaling systems. The study of these systems has yielded new surprises. One hurdle in these efforts has been that signal transduction pathways have frequently been defined in the generic absence of their tissue-specific or cell-interaction specific context.

Probes the molecular pathways and the intersection of signaling networks which are frequently deregulated in human cancers Describes EGF receptor in a tumor tissue specific context Illustrates the many ways in which EGF receptors contribute to abnormal survival and migration signaling in cancer cells and to epithelial-to-mesenchymal transition and metastasis

Contenu
EGFR Signaling Networks.- EGFR Receptor Family Extracellular Domain Structures and Functions.- EGFR family heterodimers in cancer pathogenesis and treatment.- Structure-function of EGFR kinase domain and its inhibitors.- Internalization and degradation of EGF receptor.- Differential dependence of EGFR and ErbB2 on the molecular chaperone Hsp90.- Activation of STATs 3 and 5 Through the EGFR Signaling Axis.- The intersection of EGFR and the Ras signaling pathway.- PHOSPHOINOSITIDE 3-KINASE ENZYMES AS DOWNSTREAM TARGETS OF THE EGF RECEPTOR.- Convergence of EGF Receptor and Src Family Signaling Networks in Cancer.- A Molecular Crosstalk between E-cadherin and EGFR Signaling Networks.- Crosstalk Between Insulin-like Growth Factor (IGF) and Epidermal Growth Factor (EGF) Receptors.- Negative regulation of signaling by the EGFR family.- Nuclear ErbB Receptors: Pathways and Functions.- Temporal Dynamics of EGF Receptor Signaling by Quantitative Proteomics.- Computational and Mathematical Modelling of the EGF Receptor System.- EGFR in Tumorigenesis and EGFR Tyrosine Kinase Inhibitors in Cancer Therapy.- Expression and prognostic significance of the EGFR in solid tumors.- Signalling by the EGF receptor in human cancers: accentuate the positive, eliminate the negative.- EGFR signaling in invasion, angiogenesis and metastasis.- Constitutive activation of truncated EGF receptors in glioblastoma.- EGFR Mutations, Other Molecular Alterations Related To Sensitivity to EGFR Inhibitors, and Molecular Testing for EGFR-Targeted Therapies in Non-Small Cell Lung Cancer.- Crosstalk Between COX-2 and EGFR: A Potential Therapeutic Opportunity.- Cellular sensitivity to EGF receptor inhibitors.- Utilizing combinations of molecular targeted agents to sensitize tumor cells to EGFR inhibitors.