title: Effects of epidermal growth factor receptor and insulin-like growth factor 1 receptor inhibition on proliferation and intracellular signaling in cutaneous SCCHN: potential for dual inhibition as a therapeutic modality.
abstract: BACKGROUND
  Combined inhibition of epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) has been proposed as a therapy for cutaneous squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Receptor expression and downstream signaling were assessed in cutaneous squamous cell carcinoma (SCC) cell lines and patient samples. EGFR and IGF-1R signaling was inhibited in cutaneous SCC cell lines using erlotinib and/or picropodophyllin.
  
  
  RESULTS
  EGFR and IGF-1R were overexpressed in cutaneous SCCHN specimens relative to normal skin. Dual inhibition of both receptors prevented cell growth and decreased activation of Akt and p42/44 mitogen-activated protein kinase (MAPK) more effectively than either inhibitor alone.
  
  
  CONCLUSIONS
  Dual inhibition of EGFR and IGF-1R is effective at blocking cell growth, and is correlated with inhibition of Akt and p42/44 MAPK, suggesting that this may be a promising treatment for cutaneous SCCHN.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Clayburgh
authors.forename: Neil D
authors.initials: ND
authors.lastname: Gross
authors.forename: Charlotte
authors.initials: C
authors.lastname: Proby
authors.forename: Jade
authors.initials: J
authors.lastname: Koide
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Wong
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000037:antagonists & inhibitors*; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C415032:picropodophyllin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011034:Podophyllotoxin