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Convergence of EGF Receptor and Src Family Signaling Networks in Cancer

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EGFR Signaling Networks in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

EGF receptor (EGFR) and c-Src are tyrosine kinases of the receptor and non-receptor classes, respectively, that which are frequently co-overexpressed or co-activated in multiple human cancers, including those of breast, prostate, lung, and colon. Most of these cancers express non-mutated forms of each kinase, and overexpression of either is weakly or non-oncogenic. However, When co-overexpressed, however, they exhibit profound synergism that up-regulates many neoplastic processes, including cell proliferation, survival, and metastasis. This synergism is dependent upon or greatly enhanced by physical association between c-Src and ligand-stimulated EGFR, which leads to activation of both kinases, phosphorylation of EGFR by c-Src, and enhanced phosphorylation of EGFR and c-Src substrates. Non-EGFR ligands, such as agonists for G-protein coupled receptors and cytokine receptors, also induce association between EGFR and c-Src and subsequent oncogenic consequences of this interaction. Because of their important roles in the etiology and progression of a broad spectrum of cancers, EGFR and c-Src represent signaling molecules that are ripe for combinatorial therapeutic targeting.

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Authors and Affiliations

  1. Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, VA

    Jessica E. Pritchard

  2. Biology Department, Lynchburg College, Lynchburg, VA

    Allison B. Jablonski Ph.D.

  3. Department of Microbiology, University of Virginia Health System, Charlottesville, VA, P O Box 800734, 22908

    Sarah J. Parsons Ph.D.

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  1. Jessica E. Pritchard
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  2. Allison B. Jablonski Ph.D.
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  3. Sarah J. Parsons Ph.D.
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Editors and Affiliations

  1. OSI Pharmaceuticals, Inc., Bioscience Park Drive 1, Farmingdale, 11735, U.S.A.

    John D. Haley

  2. Dept. Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom

    William John Gullick

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© 2008 Humana Press, a part of Springer Science+Business Media, LLC

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Pritchard, J.E., Jablonski, A.B., Parsons, S.J. (2008). Convergence of EGF Receptor and Src Family Signaling Networks in Cancer. In: Haley, J., Gullick, W. (eds) EGFR Signaling Networks in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-356-1_9

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  • DOI: https://doi.org/10.1007/978-1-59745-356-1_9

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