EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Cultures
2.3. Genetic Characterization of HNSCC Cell Lines and Patient Samples
2.4. Cell Proliferation Assay
2.5. Flow Cytometry
2.6. EGFR Phosphorylation Assay
2.7. Antibody-Dependent Cellular Cytotoxicity Assay
2.8. Animal Experiments
2.9. Clinical Data Analysis
2.10. Immunohistochemistry
2.11. Statistical Analysis
3. Results
3.1. EGFRvIII and R521K Genotypes
3.2. EGFR Expression Variances among the Used HNSCC Cell Lines
3.3. Cetuximab Sensitivity of HNSCC Cells in Vitro
3.4. Human HNSCC Cell Line-Derived Xenograft Growth
3.5. Immunophenotype in Wild-Type and EGFR R521 Tumor Samples and Its Correlation with Clinical Cetuximab Efficacy
3.6. Clinical Impact of EGFR R521K Status on Cetuximab Therapy Outcome
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
EGFR | epidermal growth factor receptor |
ADCC | antibody-dependent cellular cytotoxicity |
NK | natural killer |
5-FU | 5-fluorouracil |
HNSCC | head and neck squamous cell carcinoma |
PD-L1 | programmed death-ligand 1 |
EPF | Erbitux-platinum-5-FU combination therapy |
EMT | epithelial–mesenchymal transition |
PFS | progression-free survival |
OS | overall survival |
HPV | human papillomavirus |
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Patients | Total 103 | EGFR wt 62 (60%) | EGFR R521K 41 (40%) | p |
---|---|---|---|---|
Men (n, %) Women (n, %) | 81 (79%) 22 (21%) | 54 (87%) 8 (13%) | 27 (66%) 14 (34%) | p < 0.05 |
Age (median, years) | 59.5 | 60 | 58 | No correlation |
Overall response rate (n, %) | 59 (57%) | 39 (63%) | 20 (49%) | No correlation |
Disease control rate (n, %) | 89 (86%) | 52 (84%) | 37 (90%) | No correlation |
Progression-free survival (median, weeks) | 29 | 29 | 28 | No correlation |
Overall survival (median, weeks) | 50 | 48 | 49 | No correlation |
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Cserepes, M.; Nelhűbel, G.A.; Meilinger-Dobra, M.; Herczeg, A.; Türk, D.; Hegedűs, Z.; Svajda, L.; Rásó, E.; Ladányi, A.; Csikó, K.G.; et al. EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer. Cancers 2022, 14, 2407. https://doi.org/10.3390/cancers14102407
Cserepes M, Nelhűbel GA, Meilinger-Dobra M, Herczeg A, Türk D, Hegedűs Z, Svajda L, Rásó E, Ladányi A, Csikó KG, et al. EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer. Cancers. 2022; 14(10):2407. https://doi.org/10.3390/cancers14102407
Chicago/Turabian StyleCserepes, Mihály, Györgyi A. Nelhűbel, Mónika Meilinger-Dobra, Adrienn Herczeg, Dóra Türk, Zita Hegedűs, Laura Svajda, Erzsébet Rásó, Andrea Ladányi, Kristóf György Csikó, and et al. 2022. "EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer" Cancers 14, no. 10: 2407. https://doi.org/10.3390/cancers14102407