title: Molecular markers of response and resistance to EGFR inhibitors in head and neck cancers.
abstract: Receptor tyrosine kinases (RTK) are key targets for novel cancer therapeutics since they activate multiple oncogenic signalling pathways. Also, they are inherently 'druggable' due to their small ATP-dependent kinase domains (inhibitable by small molecules) and cell surface location which renders them accessible to monoclonal antibody-based therapies. The epidermal growth factor receptor (EGFR) is overexpressed in the majority of SCCHN cases and this review focuses primarily on the progress made in targeting the EGFR for the therapy of SCCHN by both small molecules and antibody-based therapies. We then discuss the overlapping and distinct molecular markers of response, innate or acquired resistance to each modality, and how these may be overcome. We also consider other RTKs overexpressed in this disease that may impact on responses and/or provide additional targets for combination therapy.
authors.affiliation: Tumour Biology and Metastasis Team, CR-UK Cancer Therapeutics Unit, McElwain Laboratories, The Institute of Cancer Research, Cotswold Road, Belmont, Sutton, Surrey, SM2 5NG, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Box
authors.forename: Miriam
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Suzanne
authors.initials: S
authors.lastname: Eccles
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068818:Cetuximab; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077544:Panitumumab; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; D047428:Protein Kinase Inhibitors; D000077544:Panitumumab; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1; D040262:Receptors, Vascular Endothelial Growth Factor; D000068818:Cetuximab