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The Role of HGF/c-MET in Head and Neck Squamous Cell Carcinoma

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Molecular Determinants of Head and Neck Cancer

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a formidable challenge to physicians, scientists, and patients. New targets that can be exploited to improve the outcome of patients afflicted with this dreadful disease are desperately needed: one such potential target is c-MET. The c-MET receptor tyrosine kinase, also known as hepatocyte growth factor receptor (HGFR), is robustly overexpressed and sometimes mutated or amplified in head and neck cancer cells, while overexpression of its ligand, hepatocyte growth factor/scatter factor (HGF/SF), often occurs in tumor-adjacent mesenchymal cells, providing paracrine signals that support tumor growth. Activation of c-MET stimulates numerous downstream signaling pathways that contribute to tumor growth, including GRB2/RAS, PI3K, STAT3, SRC, β-catenin, and Notch. Overexpression or anomalous activation of c-MET is often associated with resistance to targeted therapies inhibiting receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR), that communicate to similar growth factor cascades. In this review, we emphasize the role of c-MET/HGF in HNSCC as well as the potential for therapeutic targeting of this receptor.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology, The University of Chicago, 5841 South Maryland Avenue, 60637, Chicago, IL, USA

    Tanguy Y. Seiwert

  2. Developmental Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, 19111, Philadelphia, PA, USA

    Tim N. Beck

  3. Program in Molecular and Cell Biology and Genetics, Drexel University College of Medicine, 2900 Queen Lane, 19129, Philadelphia, PA, USA

    Tim N. Beck

  4. The University of Chicago Comprehensive Cancer Center, 5841 South Maryland Avenue, 60637, Chicago, IL, USA

    Tanguy Y. Seiwert & Ravi Salgia

Authors
  1. Tanguy Y. Seiwert
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  2. Tim N. Beck
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  3. Ravi Salgia
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Correspondence to Tanguy Y. Seiwert .

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Editors and Affiliations

  1. Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Barbara Burtness

  2. Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Erica A. Golemis

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Seiwert, T., Beck, T., Salgia, R. (2014). The Role of HGF/c-MET in Head and Neck Squamous Cell Carcinoma. In: Burtness, B., Golemis, E. (eds) Molecular Determinants of Head and Neck Cancer. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8815-6_5

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