We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
PI3K/PTEN/AKT/mTOR polymorphisms: Association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab-docetaxel.
- Authors
Pfisterer, Katharina; Fusi, Alberto; Klinghammer, Konrad; Knödler, Maren; Nonnenmacher, Anika; Keilholz, Ulrich
- 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). Conclusion 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. © 2014 Wiley Periodicals, Inc. Head Neck 37: 471-478, 2015
- Subjects
SINGLE nucleotide polymorphisms; CANCER treatment; SQUAMOUS cell carcinoma; HEAD &; neck cancer patients; CETUXIMAB; DOCETAXEL; HEALTH outcome assessment; PTEN protein
- Publication
Head & Neck, 2015, Vol 37, Issue 4, p471
- ISSN
1043-3074
- Publication type
Article
- DOI
10.1002/hed.23604