EGFR Signaling Networks in Cancer Therapy

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.

List of contents

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.

Summary

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.

Additional text

From the reviews:
"This book describes the state of EGFR antagonist development and treatment modalities…. This will be of interest to those in academic research studying EGFR signaling and/or cancer. … This is an excellent reference for those focused on a particular aspect of EGFR signaling who are looking for a concise review. This is a timely review of an increasingly complex area of study." (James P. Luyendyk, Doody’s Review Service, January, 2009)
"This book bridges the basic and clinical progress in EGFR network in cancer therapy over 40 years of EGFR research. Due to the contributors’ basic science and clinical backgrounds, the book is … best suited for basic scientists, translational scientists, and oncologists who engage in EGFR associated research and clinical therapy at various levels. The book provides a comprehensive EGFR resource for researchers not only in basic biological fields but also in preclinical and clinical therapy … ." (Guolin Zhang and Eric B. Haura, Cancer Control, Vol. 16 (4), October, 2009)
“This book is a collection of articles from different authors organized into two sections. … a good and useful book for any medicinal chemist working in this field … . all chapters are well written, clear, and rather agreeable to read. … easily understood by even an inexperienced reader. … a useful introduction to the role of EGFR signaling networks in a large number of tumors for novice researchers, but it could also be considered in some way a reference text for more experienced ones.” (Adriano Martinelli, ChemBioChem, Vol. 5, 2010)

Report

From the reviews:

"This book describes the state of EGFR antagonist development and treatment modalities.... This will be of interest to those in academic research studying EGFR signaling and/or cancer. ... This is an excellent reference for those focused on a particular aspect of EGFR signaling who are looking for a concise review. This is a timely review of an increasingly complex area of study." (James P. Luyendyk, Doody's Review Service, January, 2009)
"This book bridges the basic and clinical progress in EGFR network in cancer therapy over 40 years of EGFR research. Due to the contributors' basic science and clinical backgrounds, the book is ... best suited for basic scientists, translational scientists, and oncologists who engage in EGFR associated research and clinical therapy at various levels. The book provides a comprehensive EGFR resource for researchers not only in basic biological fields but also in preclinical and clinical therapy ... ." (Guolin Zhang and Eric B. Haura, Cancer Control, Vol. 16 (4), October, 2009)
"This book is a collection of articles from different authors organized into two sections. ... a good and useful book for any medicinal chemist working in this field ... . all chapters are well written, clear, and rather agreeable to read. ... easily understood by even an inexperienced reader. ... a useful introduction to the role of EGFR signaling networks in a large number of tumors for novice researchers, but it could also be considered in some way a reference text for more experienced ones." (Adriano Martinelli, ChemBioChem, Vol. 5, 2010)

Product details

• Assisted by: Joh D Haley (Editor), John D Haley (Editor), William John Gullick (Editor), John D Haley (Editor), John D. Haley (Editor), John Gullick (Editor), John Gullick (Editor)
• Publisher: Springer, Berlin
• Languages: English
• Product format: Paperback / Softback
• Released: 25.10.2010
• EAN: 9781617378539
• ISBN: 978-1-61737-853-9
• No. of pages: 395
• Dimensions: 178 mm x 22 mm x 254 mm
• Weight: 772 g
• Illustrations: XI, 395 p.
• Series: Cancer Drug Discovery and Development; Cancer Drug Discovery and Development
• Subjects: Natural sciences, medicine, IT, technology > Medicine > Non-clinical medicine; B, Medicine, INTERNAL MEDICINE, Oncology, Cancer Research, Biomedical Research