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  • Review Article
  • Published:

Molecular therapy in head and neck oncology

Nature Reviews Clinical Oncology volume 6, pages 266–277 (2009)Cite this article

Abstract

Therapeutic management of locally advanced, recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is often limited by a rather unfavorable efficacy and toxicity ratio. Since the 1990s, targeted molecular therapy has been extensively investigated both as a single modality and in combination with cytotoxic treatments, such as radiotherapy or chemotherapy. EGFR is commonly over expressed in HNSCC and is an attractive molecular target. The EGFR signaling pathway is involved in a variety of cellular responses including cell growth and proliferation, and monoclonal antibodies and small-molecule inhibitors have been developed to inhibit EGFR pathways. Agents that target angiogenesis have also been tested in combination with EGFR inhibitors. A number of phase I/II and phase III studies have demonstrated that patients with high-risk HNSCC or those receiving palliative treatment for recurrent or metastatic disease benefit from the addition of EGFR inhibitors to chemotherapy and radiotherapy. This Review discusses the rationale for using targeted therapies based on inhibition of EGFR and angiogenesis, and describes the most recent preclinical and clinical evidence of the important role for targeted therapies in the management of head and neck cancers.

Key Points

  • On the basis of phase III data in patients with locally advanced HNSCC, coadministration of chemotherapy and radiotherapy yields higher rates of local control and survival than radiotherapy alone, but it is also considerably more toxic

  • Upregulation of EGFR signaling has an important role in the growth and metastasis of a wide range of tumors and is overexpressed in more than 90% of HNSCC

  • Monoclonal antibodies against EGFR and small-molecule tyrosine kinase inhibitors inhibit tumor growth, invasion and metastasis, DNA damage repair, and angiogenesis

  • In patients with locally advanced disease, cetuximab plus radiation significantly improves the median duration of locoregional control and overall survival, compared with radiation alone

  • The use of agents that target the outer and inner domains of EGFR is under investigation

  • Upregulation of VEGF levels by EGFR activation and cytotoxic agents justifies the use of molecular therapies that target both EGFR and VEGF

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Authors and Affiliations

  1. Department of Radiation Oncology, Genolier Swiss Medical Network, Genolier, Switzerland

    Jacques Bernier

  2. Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Søren M. Bentzen

  3. Department of Medical Oncology, University Hospital Antwerp, Edegem, Belgium

    Jan B. Vermorken

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  1. Jacques Bernier
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  2. Søren M. Bentzen
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  3. Jan B. Vermorken
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Correspondence to Jacques Bernier.

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Competing interests

Jacques Bernier is a consultant for Amgen, GlaxoSmithKline, Merck Serono and Sanofi–Aventis, and is also on the speakers bureau for Amgen, Merck Serono and Sanofi–Aventis. Jan B. Vermorken is a consultant and is on the speakers bureau for Amgen, Merck Serono and Sanofi–Aventis. Søren M. Bentzen declared no competing interests.

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Bernier, J., Bentzen, S. & Vermorken, J. Molecular therapy in head and neck oncology. Nat Rev Clin Oncol 6, 266–277 (2009). https://doi.org/10.1038/nrclinonc.2009.40

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