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EGFR Signaling and Radiation

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Molecular Determinants of Radiation Response

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

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Abstract

The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase that is over expressed or mutated in a broad spectrum of epithelial cancers and serves as an important regulator of oncogenesis. Aberrant EGFR expression and activity have been associated with uncontrolled cancer cell proliferation and survival. Therefore, EGFR has been considered an attractive target in cancer therapy, including studies investigating the ability of EGFR signaling to modulate radiation response. Two primary classes of EGFR inhibitors have been developed in recent years: monoclonal antibodies (mAbs) and tyrosine kinase inhibitors. The most mature clinical data to date derives from studies with the anti-EGFR mAb inhibitor cetuximab combined with radiation in head and neck squamous cell carcinoma (HNSCC) that has provided a new therapeutic option for this disease. Postulated mechanisms of interaction between these two modalities include effects on cell cycle distribution, apoptosis, tumor cell repopulation, DNA damage/repair, and impact on tumor vasculature. The improvement in tumor control rates and overall survival in HNSCC has prompted investigation of this approach in other tumor types. Here we review pertinent literature regarding the interaction of anti-EGFR therapies with radiation, including preclinical and clinical trial data reflecting promising future directions for this approach.

Disclosure: PMH has held active laboratory research agreements with industry sponsors developing EGFR inhibitors including Amgen, AstraZeneca, Genentech, and ImClone within the last 5 years.

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Acknowledgements

Supported by NIH/NCI Grant R01 CA 113448 to PMH; EFD supported by NIH Physician Scientist Training in Cancer Medicine.

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Authors and Affiliations

  1. Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, K4/332, 600 Highland Avenue, Madison, WI, 53792, USA

    Emily F. Dunn

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  1. Emily F. Dunn
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  2. Shyhmin Huang
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  3. Paul M. Harari
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Correspondence to Emily F. Dunn .

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  1. Dept. Radiation Oncology, Johns Hopkins University, N. Wolfe Street 600, Baltimore, 21287, Maryland, USA

    Theodore L. DeWeese

  2. Dept. Radiation Oncology, Johns Hopkins University, Orleans Street 1550, Baltimore, 21231, Maryland, USA

    Marikki Laiho

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Dunn, E.F., Huang, S., Harari, P.M. (2011). EGFR Signaling and Radiation. In: DeWeese, T., Laiho, M. (eds) Molecular Determinants of Radiation Response. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8044-1_10

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