title: DNA aneuploidy-specific therapy for head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Patients with head and neck squamous cell carcinoma (HNSCC) have an unfavorable prognosis, with a 5-year survival rate of approximately 40%. Genetic analyses have revealed that the majority of HNSCCs carry complex, aneuploid karyotypes, showing numerical and structural chromosomal imbalances. New compounds are being developed that target chromosomal instability in general, specifically affecting cells with aneuploid karyotypes.
  
  
  METHODS
  Two such compounds, 5-aminoimidazole-4-carboxamide riboside (AICAR) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), were tested using a panel of stable diploid and unstable aneuploid HNSCC cell lines, and short-term cultures of normal keratinocytes as control.
  
  
  RESULTS
  A significant growth inhibitory effect by both compounds was observed in the aneuploid compared to diploid HNSCC cell lines and to the normal keratinocytes. This effect was independent from the TP53 mutation status. Combination treatment with AICAR and 17-AAG demonstrated the strongest inhibition.
  
  
  CONCLUSIONS
  Aneuploidy-targeted therapy may be a viable addition to the treatment options for HNSCC.
authors.affiliation: Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: García Martínez
authors.affiliation: Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Inclán
authors.affiliation: Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Llorente
authors.affiliation: Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Hermsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000782:Aneuploidy; D016227:Benzoquinones / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D015603:Keratinocytes; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D020125:Mutation, Missense; D012263:Ribonucleosides / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D012263:Ribonucleosides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000620:Aminoimidazole Carboxamide; C112765:tanespimycin; C011651:acadesine
keywords: aneuploidy; cancer therapy; chromosomal instability; head and neck squamous cell carcinoma; tumor cell line