A patient-derived somatic mutation in the epidermal growth factor receptor ligand-binding domain confers increased sensitivity to cetuximab in head and neck cancer

摘要: Abstract Background Cetuximab is an epidermal growth factor receptor (EGFR)-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma (HNSCC) metastatic colorectal cancer, but no predictive biomarkers activity have yet identified. Establishment such will help identify a subset benefit from cetuximab therapy. Methods In this paper, we report on patient HNSCC who had complete tumour regression following given as single agent after initial surgery radiation The EGFR protein expression level, gene copy number sequence were assessed both normal tissues. Results Besides overexpression amplification in tissue, sequencing revealed presence two somatic mutations, one kinase domain (R705G) other ligand binding (P546S). Cells stably express these mutants treated their sensitivity to drug was compared cells expressing wildtype gene. While P546S mutation sensitised NIH-3T3 cetuximab, R705G marginal effect. double mutant (P546S/R705G) behaved like mutant, indicating does not contribute increased cetuximab. No mutations found K-RAS or B-RAF genes HPV DNA detected tumour. This first may Conclusions Our results support role sensitivity. Other factors including high also contributed observed response. severity skin rash developed by its correlation antitumour exclude involvement immune system (i.e. complement-mediated response) well. occurrence needs be evaluated HNSCC, well prospective evaluation anti-tumour tumours harbouring mutation.