Abstract
BackgroundBased on expression data, Epidermal Growth Factor Receptor (EGFR) emerged as therapeutic target in Head and Neck Cancer but clinical efficacy of EGFR inhibitors was very limited. We reinvestigated the EGFR expression and activation status necessary for response in cell lines and compared that to clinical samples.MethodsClinical samples of head and neck squamous cell carcinoma (HNSCC, n=63), mostly from late stage (IV) and poorly or undifferentiated character and cultured cell lines (n=14) were tested by immunohistochemistry (IHC) (n=55) and sandwich immunoassays (n=63) for expression and phosphorylation of EGFR (Tyrosine-1173). Response of 14 different HNSCC cell lines to Erlotinib was tested in proliferation assays.ResultsMost HNSCC cell lines respond to Erlotinib. EGFR is phosphorylated in these cell lines. Resistant cell lines display very low level EGFR expression and phosphorylation. EGFR activity in clinical samples is significantly below that observed in cell lines. In clinical samples, EGFR is not overexpressed on the single cellular level. We show similar levels of EGFR expression in growing keratinocytes and tumor cells.ConclusionsCell lines are not representative of the clinical situation in HNSCC. Larger studies should investigate whether patient subgroups with activating EGFR mutations or overexpression can be identified.
Highlights
Squamous cell carcinomas of the upper aerodigestive tract, usually summarized as head and neck squamous cell carcinoma (HNSCC), represent the sixth most common cancer in the world [1]
Most HNSCC cell lines respond to Erlotinib
Two of the HNSCC cell lines did not show a clear response at 3 μM Erlotinib
Summary
Squamous cell carcinomas of the upper aerodigestive tract, usually summarized as head and neck squamous cell carcinoma (HNSCC), represent the sixth most common cancer in the world [1]. Based on its broad expression in up to 90% of the HNSCC cases, epidermal growth factor receptor emerged as potential target for targeted therapies [3]. No predictive value for Cetuximab use could be derived from data on EGFR copy number, protein expression or mutation [7, 8]. This is in line with the broad expression of EGFR and antibody dependent cellular cytotoxicity (ADCC) as mode of action. Epidermal Growth Factor Receptor (EGFR) emerged as therapeutic target in Head and Neck Cancer but clinical efficacy of EGFR inhibitors was very limited. We reinvestigated the EGFR expression and activation status necessary for response in cell lines and compared that to clinical samples
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
