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Current aspects of targeted therapy in head and neck tumors

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Abstract

This review focuses on the current and upcoming options of targeted therapy (biologicals) in head and neck squamous cell carcinoma (HNSCC) with special regard to conceptual integration in future strategies. Epidermal growth factor receptor (EGFR) is the most prominent candidate for therapeutic targeting because of its more than 90% expression rate in HNSCC and influence on the regulation of proliferation, apoptosis, metastasis, angiogenesis and cell differentiation. The point of view of head and neck surgeons is mainly adjusted to reach a balance between targeted, minimal ablative surgery and the evidence-based demand of oncologic accurate surgery with clear margins and, if needed, adjuvant or primary systemic chemoradiation. Therefore, the long-term effects of chemoradiation regimens, such as dysphagia, aspiration and laryngeal immobility caused by fibrosis, are just beginning to be studied and are becoming one of the major problems in the ongoing treatment of HNSCC. In this context, molecular targeting biologicals with a different toxicity profile and hopefully less late damage to functionally important tissues may open new strategies in primary and adjuvant treatment of HNSCC. Besides cetuximab and other EGFR targeting mAbs, this review focuses on receptor and non-receptor tyrosine kinase inhibitors, which further might play a role in the future treatment of HNSCC. To complete the current picture, the problem of multi drug resistance in cancer progenitor cells, targeting members of several relevant pathways and novel agents like pemetrexed and enzastaurin, are discussed in a broader sense of targeted therapy.

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Abbreviations

KIT:

Stem cell factor (SCF) receptor

GSI-18:

[11-Endo]-N(5,6,7,8,9,10-hexahydro-6,9-methanobenzo[a][8]annulen-11-ylthiophene-2-sulfonamide

MDR1:

Multidrug resistance 1

MRP1:

Multidrug resistance-associated protein 1

MRP2:

Multidrug resistance-associated protein 2

NF-κB:

Nuclear factor-κB

PDGFR:

Platelet-derived growth factor receptor

Pgp:

P-glycoprotein

PI3K:

Phosphatidylinositide-3′-kinase

TKI:

Tyrosine kinase inhibitor

VEGF:

Vascular epithelial growth factor

VEGFR:

Vascular epithelial growth factor receptor

WIF-1:

Wingless inhibitory factor-1

Wnt:

Wingless ligand

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Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Leipzig, Germany

    Andreas Dietz, Andreas Boehm, Christian Mozet & Gunnar Wichmann

  2. Institute of Organic Chemistry, University of Leipzig, Leipzig, Germany

    Athanassios Giannis

  3. Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde/Plastische Operationen, Universität Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany

    Andreas Dietz

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Dietz, A., Boehm, A., Mozet, C. et al. Current aspects of targeted therapy in head and neck tumors. Eur Arch Otorhinolaryngol 265 (Suppl 1), 3–12 (2008). https://doi.org/10.1007/s00405-008-0697-6

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