title: PI3K/PTEN/AKT/mTOR polymorphisms: association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab-docetaxel.
abstract: BACKGROUND
  The purpose of this study was to determine whether single nucleotide polymorphisms (SNPs) in AKT1, AKT2, FRAP1, PIK3CA, and PTEN were associated with treatment response and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Genomic DNA was extracted from formalin-fixed tissue of 45 patients with recurrent or initially metastatic HNSCC, and SNPs were genotyped by means of real-time polymerase chain reaction (PCR) system or direct sequencing.
  
  
  RESULTS
  The AKT2:rs8100018 and the PTEN:rs12569998 homozygous variants resulted as associated with an increased risk of progression (hazard ratio [HR], 4.83; 95% confidence interval [CI], 1.11-21.03; and HR, 2.36; 95% CI, 1.24-4.50, respectively). An additive effect on risk of progression was observed. The AKT2:rs8100018 homozygous variant was significantly associated with a higher risk of death (HR, 3.57; 95% CI, 1.06-12.00), whereas the presence of at least one variant allele of AKT1:rs3803304 was associated with a lower risk of death (HR, 0.51; 95% CI, 0.27-0.97).
  
  
  CONCLUSIONS
  We identified combined genotypes associated with outcome of HNSCC, which might have an impact for identification of a target population for cetuximab-docetaxel treatment. Results should be considered as an initial finding and warrant validation in larger clinical trials.
authors.affiliation: Department of Hematology and Medical Oncology, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pfisterer
authors.forename: Alberto
authors.initials: A
authors.lastname: Fusi
authors.forename: Konrad
authors.initials: K
authors.lastname: Klinghammer
authors.forename: Maren
authors.initials: M
authors.lastname: Knödler
authors.forename: Anika
authors.initials: A
authors.lastname: Nonnenmacher
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000556:secondary; D000068818:Cetuximab / Q000627:therapeutic use*; D058534:Class I Phosphatidylinositol 3-Kinases; D000077143:Docetaxel; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000556:secondary; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068818:Cetuximab; D058534:Class I Phosphatidylinositol 3-Kinases; D000077143:Docetaxel; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D043823:Taxoids; C546842:MTOR protein, human; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C494929:PTEN protein, human
keywords: AKT; cetuximab; head and neck; single nucleotide polymorphism (SNP); squamous cell carcinoma