title: Cytotoxic effect of lapatinib is restricted to human papillomavirus-positive head and neck squamous cell carcinoma cell lines.
abstract: BACKGROUND
  Lapatinib is a dual epidermal growth factor receptor (EGFR) and HER2 inhibitor. Overexpression of these receptors is frequently observed in head and neck squamous cell carcinoma (HNSCC). As growing proportion of HNSCC is characterized by human papillomavirus (HPV) infection, we aimed at evaluating the efficacy of lapatinib as function of HPV status in HNSCC cell lines.
  
  
  METHODS
  Two HPV-positive and two HPV-negative HNSCC cell lines were used. Proliferation, cell cycle, and Annexin V assays were performed to test their sensitivity to lapatinib. Combination of lapatinib and ionizing radiation was evaluated with clonogenic survival assays. Akt, EGFR and HER2, and E6/E7 expression and activation were analyzed by immunoblotting and quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Lapatinib reduced E6 and E7 expression and Akt phosphorylation, inhibited cell proliferation and induced cell death in HPV-positive cell lines. An additive effect of lapatinib with radiation was observed in these cells. Lapatinib had no effect on HPV-negative cells.
  
  
  CONCLUSIONS
  Lapatinib efficacy restricted to the HPV-positive cells suggests that HPV status could be a potential marker for enhanced response to lapatinib in HNSCC.
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France ; Radiation Therapy Department, Oscar Lambret Comprehensive Cancer Center, Lille, France.
authors: Ingrid
authors: I
authors: Fumagalli
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France.
authors: Delphine
authors: D
authors: Dugue
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France ; Radiation Therapy Department, Oscar Lambret Comprehensive Cancer Center, Lille, France.
authors: Jean Emmanuel
authors: JE
authors: Bibault
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France.
authors: Céline
authors: C
authors: Clémenson
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France.
authors: Marie Catherine
authors: MC
authors: Vozenin
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France.
authors: Michele
authors: M
authors: Mondini
authors: Inserm U1030, Molecular Radiotherapy, LABEX LERMIT, Gustave Roussy, University Paris XI, Villejuif, France ; Department of Radiation Oncology, Gustave Roussy, University Paris XI, Villejuif, France.
authors: Eric
authors: E
authors: Deutsch
keywords: EGFR; HER2; HPV; ionizing radiation; lapatinib; tyrosine kinase inhibitor