PI3K/PTEN/AKT/mTOR polymorphisms: Association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab-docetaxel

• Published in: Head & neck Vol. 37; no. 4; pp. 471 - 478
• Main Authors: Pfisterer, Katharina, Fusi, Alberto, Klinghammer, Konrad, Knödler, Maren, Nonnenmacher, Anika, Keilholz, Ulrich
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.04.2015; Wiley Subscription Services, Inc
• Subjects: Aged; AKT; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - secondary; cetuximab; Cetuximab - therapeutic use; Class I Phosphatidylinositol 3-Kinases; Docetaxel; Female; Genotype; head and neck; Head and Neck Neoplasms - secondary; Humans; Male; Middle Aged; Neoplasm Recurrence, Local - genetics; Phosphatidylinositol 3-Kinases - genetics; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-akt - genetics; PTEN Phosphohydrolase - genetics; single nucleotide polymorphism (SNP); squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Taxoids - therapeutic use; TOR Serine-Threonine Kinases - genetics; Treatment Outcome; cetuximab; head and neck; AKT; single nucleotide polymorphism (SNP); squamous cell carcinoma
• ISSN: 1043-3074; 1097-0347
• DOI: 10.1002/hed.23604

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