Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 6003-6003 ◽  
Author(s):  
T. Y. Seiwert ◽  
E. E. Cohen ◽  
X. Wang ◽  
M. Kocherginsky ◽  
M. Bhayani ◽  
...  
Tumor Biology ◽  
2016 ◽  
Vol 37 (10) ◽  
pp. 13435-13443 ◽  
Author(s):  
B. Cirauqui ◽  
M. Margelí ◽  
V. Quiroga ◽  
A. Quer ◽  
N. Karachaliou ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6033-6033
Author(s):  
T. Seiwert ◽  
D. T. Weaver ◽  
X. Wang ◽  
J. Kutok ◽  
E. Cohen ◽  
...  

6033 Background: Concurrent chemoradiotherapy is a standard-of-care for head and neck cancer. Radiotherapy and chemotherapeutic agents damage DNA; lack of adequate repair induces tumor cell death. The network of DNA repair pathways was examined to predict TFHX chemoradiotherapy outcomes. Methods: Biopsy specimens (paraffin) from 60 HNC patients were evaluated from tissue microarrays. Samples originated from patient groups from phase I/II studies: 1) poor-prognosis radiation-naïve, 2) re-irradiation. All were treated with TFHX-based chemoradiotherapy. DNA repair biomarkers XPF, pMK2, PAR, pH2AX, FANCD2, ATM, BRCA1, RAD51, ERCC1 (clone 8F1), and p53 were explored using IHC, automated image processing, and machine reading (>500 cells/read), for nuclear and cytoplasmic quantity, area, and intensity, and correlated with clinical outcome. Results: There was low inter-core variability per tumor with median patient ranking signal to noise ratio of 15.0 across all markers. Patients were stratified into short and long survival groups by determination of critical marker thresholds. Five DNA repair biomarkers (RAD51, ATM, BRCA1, XPF, FANCD2) exhibited univariate significance for overall survival (p = 2.65e-3, 1.53e-2, 4.77e-4, 8.57e-5, 1.32e-3)(additional clinical parameters multivariate analysis was not feasible due to sample size). ERCC1 was not statistically significant (p = 1.0). Pairwise biomarker combinations improved survival group discrimination. Combination of 4 DNA repair biomarkers (FANCD2, BRCA1, ATM, XPF) was also significant (p = 1.31e-4). Discriminant analysis demonstrated higher fractions of correctly identified patients in good/poor survival groups from four-marker tests. Conclusions: Five DNA repair biomarkers predicted overall survival following TFHX-based chemoradiotherapy. By contrast ERCC1 (8F1) was not significant. Combination of markers improved predictive ability in this study. The analysis of DNA repair pathways, particularly in homologous recombination, DNA damage response, and nucleotide excision repair, may be clinically useful. Validation in a larger, homogeneous patient population, and using platinum-based chemoradiotherapy, is indicated and currently ongoing. [Table: see text]


1999 ◽  
Vol 125 (2) ◽  
pp. 185 ◽  
Author(s):  
Erich M. Sturgis ◽  
Gary L. Clayman ◽  
Yongli Guan ◽  
Zhaozheng Guo ◽  
Qingyi Wei

2013 ◽  
Vol 43 (3) ◽  
pp. 217-224 ◽  
Author(s):  
Rim Khlifi ◽  
Imen Kallel ◽  
Bouthaina Hammami ◽  
Amel Hamza-Chaffai ◽  
Ahmed Rebai

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e17025-e17025
Author(s):  
Beatriz Cirauqui ◽  
Vanesa Quiroga ◽  
Imane Chaib ◽  
Belen Sanchez ◽  
Niki Karachaliou ◽  
...  

2008 ◽  
Vol 25 (5) ◽  
pp. 489-497 ◽  
Author(s):  
Pawel Rusin ◽  
Jurek Olszewski ◽  
Alina Morawiec-Bajda ◽  
Karolina Przybylowska ◽  
Dariusz Kaczmarczyk ◽  
...  

2012 ◽  
Vol 3 (4) ◽  
pp. 719-724 ◽  
Author(s):  
HUA YUAN ◽  
HUIZHANG LI ◽  
HONGXIA MA ◽  
YUMING NIU ◽  
YUNONG WU ◽  
...  

2016 ◽  
Vol 23 (2) ◽  
pp. 253-264 ◽  
Author(s):  
Orsolya Rusz ◽  
Margit Pál ◽  
Éva Szilágyi ◽  
László Rovó ◽  
Zoltán Varga ◽  
...  

2009 ◽  
Vol 64 (7-8) ◽  
pp. 601-610 ◽  
Author(s):  
Pawel Rusin ◽  
Anna Walczak ◽  
Anita Zwierzchlejska ◽  
Jurek Olszewski ◽  
Alina Morawiec-Bajda ◽  
...  

DNA repair is critical for successful chemo- and radiotherapy of human tumours, because their genotoxic sensitivity may vary in different types of cancer cells. In this study we have compared DNA damage and the efficiency of its repair after genotoxic treatment with hydrogen peroxide, cisplatin and γ-radiation of head and neck squamous cell carcinoma (HNSCC). Lymphocytes and tissue cells from biopsies of 37 cancer patients and 35 healthy donors as well as the HTB-43 larynx cancer cell line were employed. The cell sensitivity to genotoxic treatment was estimated by the MTT survival assay. The extent of DNA damage and efficiency of its repair was examined by the alkaline comet assay. Among the examined treatments, we found that HNSCC cells were the most sensitive to γ-radiation and displayed impaired DNA repair. In particular, DNA damage was repaired less effectively in cells from HNSCC metastasis than healthy controls. In conclusion, our results suggest that the different genotoxic sensitivity of HNSCC cells may depend on their DNA repair capacity what in turn may be connected with the effectiveness of head and neck cancer therapy.


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