: John D Haley, William John Gullick
: John D. Haley, William John Gullick
: EGFR Signaling Networks in Cancer Therapy
: Humana Press
: 9781597453561
: 1
: CHF 190.00
:
: Klinische Fächer
: English
: 395
: Wasserzeichen
: PC/MAC/eReader/Tablet
: PDF
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.
PREFACE6
TABLE8
CONTENTS8
CONTRIBUTORS10
Section I: EGFR Signaling Networks13
1 EGF Receptor Family Extracellular Domain Structures and Functions14
2 EGFR Family Heterodimers in Cancer Pathogenesis and Treatment26
3 Structure-Function of EGFR Kinase Domain and Its Inhibitors42
4 Internalization and Degradation of the EGF Receptor57
5 Differential Dependence of EGFR and ErbB2 on the Molecular Chaperone Hsp9072
6 Activation of STATs 3 and 5 Through the EGFR Signaling Axis81
7 The Intersection of EGFR and the Ras Signaling Pathway96
8 Phosphoinositide 3-Kinase Enzymes as Downstream Targets of the EGF Receptor103
9 Convergence of EGF Receptor and Src Family Signaling Networks in Cancer124
10 A Molecular Crosstalk between E-cadherin and EGFR Signaling Networks143
11 Crosstalk Between Insulin-like Growth Factor (IGF) and Epidermal Growth Factor (EGF) Receptors159
12 Negative Regulation of Signaling by the EGFR Family173
13 Nuclear ErbB Receptors: Pathways and Functions191
14 Temporal Dynamics of EGF Receptor Signaling by Quantitative Proteomics202
15 Computational and Mathematical Modeling of the EGF Receptor System211
Section II EGFR in Tumorigenesis and EGFR Tyrosine Kinase Inhibitors in Cancer Therapy221
16 Expression and Prognostic Significance of the EGFR in Solid Tumors222
17 Signaling by the EGF Receptor in Human Cancers: Accentuate the Positive, Eliminate the Negative236
18 EGFR Signaling in Invasion, Angiogenesis and Metastasis257
19 Constitutive Activation of Truncated EGF Receptors in Glioblastoma277
20 EGFR Mutations, Other Molecular Alterations Related to Sensitivity to EGFR Inhibitors, and Molecular Testing for EGFR-Targeted Therapies in Non-Small Cell Lung Cancer293
21 Crosstalk Between COX-2 and EGFR: A Potential Therapeutic Opportunity337
22 Cellular Sensitivity to EGF Receptor Inhibitors352
23 Utilizing Combinations of Molecular Targeted Agents to Sensitize Tumor Cells to EGFR Inhibitors368
Index382
Color Plate393