Journal ArticleDOI
The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification.
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TLDR
A broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention is given.Abstract:
Homeostasis of multicellular organisms is critically dependent on the correct interpretation of the plethora of signals which cells are exposed to during their lifespan. Various soluble factors regulate the activation state of cellular receptors which are coupled to a complex signal transduction network that ultimately generates signals defining the required biological response. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases represents both key regulators of normal cellular development as well as critical players in a variety of pathophysiological phenomena. The aim of this review is to give a broad overview of signal transduction networks that are controlled by the EGFR superfamily of receptors in health and disease and its application for target-selective therapeutic intervention. Since the EGFR and HER2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors, such as G-protein-coupled receptors and integrins, our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems.read more
Citations
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The oncogene HER2; Its signaling and transforming functions and its role in human cancer pathogenesis
TL;DR: An abundance of experimental evidence now solidly supports the HER2 oncogene hypothesis and etiologically links amplification of the HER1 gene locus with human cancer pathogenesis and suggests that HER2 may indeed induce cell transformation through multiple mechanisms.
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Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy.
Rama Pai,Brian A. Soreghan,Brian A. Soreghan,Imre Szabó,Imre Szabó,Meredith Pavelka,Meredith Pavelka,Dolgor Baatar,Dolgor Baatar,Andrzej S. Tarnawski,Andrzej S. Tarnawski +10 more
TL;DR: Evidence is provided that prostaglandin E2 (PGE2) rapidly phosphorylates EGFR and triggers the extracellular signal-regulated kinase 2 (ERK2)–mitogenic signaling pathway in normal gastric epithelial and colon cancer cell lines, revealing a previously unknown mechanism by which PGE2 mediates trophic actions resulting in gastric and intestinal hypertrophy as well as growth of colonic polyps and cancers.
Journal Article
Herceptin-induced Inhibition of Phosphatidylinositol-3 Kinase and Akt Is Required for Antibody-mediated Effects on p27, Cyclin D1, and Antitumor Action
F. Michael Yakes,Wichai Chinratanalab,Christoph A. Ritter,Walter King,Steven A. Seelig,Carlos L. Arteaga +5 more
TL;DR: Data suggest that changes in cell cycle- and apoptosis-regulatory molecules after HER2 blockade with Herceptin result, at least in part, from the inhibition of Akt, and disabling PI3K and Akt is required for the antitumor effect of HER2 inhibitors.
Journal ArticleDOI
Expression of the HER1–4 family of receptor tyrosine kinases in breast cancer
TL;DR: There is a strong interaction, in terms of survival, between HER expression and ER expression, and the development of HER‐targeted agents, and agents targeted at the downstream signalling pathways, therefore provides new possibilities in the treatment of breast cancer.
Journal ArticleDOI
Cetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II Trial
Henry Q. Xiong,Arthur Rosenberg,Albert LoBuglio,William Schmidt,Robert A. Wolff,John Deutsch,Michael Needle,James L. Abbruzzese +7 more
TL;DR: In this article, the combination of cetuximab and gemcitabine was used in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer.
References
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Journal ArticleDOI
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
Dennis J. Slamon,Gary M. Clark,Steven G. Wong,Wendy J. Levin,Axel Ullrich,William L. McGuire +5 more
TL;DR: Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer, and had greater prognostic value than most currently used prognostic factors in lymph node-positive disease.
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Signal transduction by receptors with tyrosine kinase activity
Axel Ullrich,Joseph Schlessinger +1 more
TL;DR: Cet article synthese montre comment des recepteurs membranaires a activite tyrosine kinase peuvent etre impliques dans la transduction and notamment jouent le role de signal de the transduction.
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Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Melody A. Cobleigh,Charles L. Vogel,Debasish Tripathy,Nicholas J. Robert,Susy Scholl,Louis Fehrenbacher,Janet M. Wolter,Virginia Paton,Steven Shak,Gracie Lieberman,Dennis J. Slamon +10 more
TL;DR: Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.
Journal ArticleDOI
Epidermal growth factor-related peptides and their receptors in human malignancies
Journal ArticleDOI
Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells
Axel Ullrich,Lisa M. Coussens,Joel S. Hayflick,Thomas J. Dull,Alane M. Gray,A W Tam,Jeffrey E. Lee,Yosef Yarden,Towia A. Libermann,Joseph Schlessinger +9 more
TL;DR: The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted ν-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains.