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EGFR-targeted therapies in the post-genomic era

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Abstract

Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials. The humanized monoclonal antibody nimotuzumab is also approved for head and neck cancers in Cuba, Argentina, Colombia, Peru, India, Ukraine, Ivory Coast, and Gabon in addition to nasopharyngeal cancers in China. Few other EGFR-targeted therapeutics for head and neck cancers have led to as significant responses as seen in lung carcinomas, for instance. Recent genome sequencing of head and neck tumors has helped identify patient subgroups with improved response to EGFR inhibitors, for example, cetuximab in patients with the KRAS-variant and the tyrosine kinase inhibitor erlotinib for tumors harboring MAPK1E322K mutations. Genome sequencing has furthermore broadened our understanding of dysregulated pathways, holding the potential to enhance the benefit derived from therapies targeting EGFR.

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Acknowledgements

This work was supported by the National Institutes of Health grants R01 DE24728 (DEJ), P50CA097190 (DEJ and JRG), and R01 DE023685 (JRG), and American Cancer Society grant CRP-13-308-06-COUN (JRG).

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  1. Department of Otolaryngology, University of California San Francisco, 2380 Sutter Street, San Francisco, CA, 94113, USA

    Mary Jue Xu, Daniel E. Johnson & Jennifer R. Grandis

  2. Clinical and Translational Science Institute, 550 16th, Street, San Francisco, CA, 94158, USA

    Jennifer R. Grandis

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  1. Mary Jue Xu
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Xu, M.J., Johnson, D.E. & Grandis, J.R. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev 36, 463–473 (2017). https://doi.org/10.1007/s10555-017-9687-8

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