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EGFR Signaling Networks in Cancer Therapy pp 245–264Cite as

EGFR signaling in invasion, angiogenesis and metastasis

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

Abstract

Tumor invasion and metastasis are the hallmarks of advanced stage cancer and are associated with poor patient prognosis. EGFR is overexpressed in a variety of tumor types and this frequently correlates with a more aggressive tumor phenotype. In this chapter, we discuss the cellular and molecular mechanisms by which EGFR contributes to tumor progression and present evidence from experimental and clinical observations that reinforce the notion that EGFR actively contributes to the onset of metastatic disease. EGFR plays a key role in the regulation of processes central to tumor invasion including cell adhesion and motility through its interactions with molecules such as integrins, cadherins, phospholipase Cγ1 and phosphoinositide 3-kinase. In addition, EGFR signaling can contribute to both proteolysis and angiogenesis through up-regulated expression of matrix metalloproteinases (MMPs) and angiogenic cytokines e.g. VEGF-A and IL-8. The significance of these contributions to tumor invasion and metastasis is highlighted by the fact that a mutant, constitutively active receptor (EGFRvIII) associated with human cancers can induce these behaviors when transfected into fibroblasts. Finally, we discuss the use of EGFR antagonists to stem metastatic disease and their potential, in combination with additional novel agents, to improve treatment for cancer patients.

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Authors and Affiliations

  1. Tumour Biology and Metastasis Team, CR-UK Centre For Cancer Therapeutics, McElwain Laboratories, Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 5NG, UK

    Carol Box PhD & Joanna Peak MSc

  2. Head and Neck Unit, Royal Marsden Hospital, Fulham Rd, London, SW3 6JJ, UK

    Susanne Rogers FRCR

  3. McElwain Laboratories, Institute of Cancer Research, 15 Cotswold Rd, Belmont, Sutton, Surrey, SM2 5NG, UK

    Suzanne Eccles Ph.D

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  4. Suzanne Eccles Ph.D
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  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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Box, C., Peak, J., Rogers, S., Eccles, S. (2008). EGFR signaling in invasion, angiogenesis and metastasis. 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_18

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