title: The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines.
abstract: OBJECTIVE
  HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells.
  
  
  METHODS
  Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay.
  
  
  RESULTS
  Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1.
  
  
  CONCLUSIONS
  PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity.
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Julian David
authors.initials: JD
authors.lastname: Güster
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stephanie Valerie
authors.initials: SV
authors.lastname: Weissleder
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Busch
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kriegs
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dikomey
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Germany; Department of Otolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Germany. Electronic address: t.rieckmann@uke.uni-hamburg.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Rieckmann
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015153:Blotting, Western / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy* / Q000821:virology; D002470:Cell Survival / Q000235:genetics; D000068818:Cetuximab; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000528:radiation effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005455:Fluorescent Antibody Technique / Q000379:methods; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000532:radiotherapy* / Q000821:virology; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics / Q000528:radiation effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: Chk1; EGFR; HNSCC; HPV; PARP; Radiosensitivity