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Published on: April 22, 2019
Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck
Mark E Sharafinski1, Robert L Ferris, Soldano Ferrone
1Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Background:
Cumulative evidence implicates the epidermal growth factor receptor (EGFR) as an important therapeutic target in head and neck squamous cell carcinoma (HNSCC). The basis for the lack of correlation between EGFR expression in the HNSCC tumor and clinical responses to EGFR inhibitors is incompletely understood. Although a variety of mechanisms likely contribute to the effectiveness of EGFR blockade, this review focuses on the biologic implications of known EGFR variations and the role of the immune system in mediating clinical responses to EGFR inhibitors.
Methods:
A Medline review of articles published in the last 10 years (1999-present) on EGFR in HNSCC was performed in combination with preliminary data from our laboratories.
Results:
Studies published to date suggest no association between the expression of EGFR on HNSCC tumors and clinical responses to EGFR inhibitors. Several mechanisms have been proposed to mediate clinical response to EGFR inhibitors in HNSCC. Cumulative results from our laboratories support the role of several mechanisms, including cellular immune activation and mutated EGFR variants, in contributing to the discrepancy between level of EGFR expression and clinical response to EGFR inhibitors.
Conclusion:
The efficacy of EGFR targeted therapies may be mediated, at least in part, by the immune system and the presence of the truncated EGFR variant, EGFRvIII, among other factors. Criteria to identify the subset of patients likely to be responsive to EGFR targeted therapies are needed.
Insights
Epidermal growth factor receptor (EGFR) inhibitors show promise in head and neck squamous cell carcinoma (HNSCC). Patient response to EGFR inhibitors may depend on immune system activation and EGFR variants, not just EGFR expression levels.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) is a key therapeutic target in head and neck squamous cell carcinoma (HNSCC).
- The correlation between EGFR expression and clinical response to EGFR inhibitors in HNSCC is not fully understood.
- This review explores EGFR variations and immune system roles in HNSCC treatment response.
Purpose of the Study:
- To investigate the biological mechanisms underlying clinical response to EGFR inhibitors in HNSCC.
- To elucidate the role of EGFR variants and the immune system in HNSCC treatment efficacy.
- To identify factors influencing patient response to EGFR-targeted therapies.
Main Methods:
- Conducted a Medline literature review of EGFR in HNSCC from 1999 to present.
- Incorporated preliminary data from laboratory investigations.
- Focused on biological implications of EGFR variations and immune system involvement.
Main Results:
- No direct association found between EGFR expression levels and clinical response to EGFR inhibitors in HNSCC.
- Cellular immune activation and mutated EGFR variants contribute to response variability.
- Laboratory data support these mechanisms in explaining the discrepancy between EGFR expression and clinical outcomes.
Conclusions:
- The immune system and EGFR variants, such as EGFRvIII, may mediate the efficacy of EGFR-targeted therapies in HNSCC.
- Further research is needed to establish criteria for identifying responsive patient subsets.
- Understanding these factors can optimize EGFR inhibitor therapy for HNSCC patients.
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