nach oben

Erschienen in:

01.12.2012 | Original Article

Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer

verfasst von: M. Provencio, C. Camps, M. Cobo, R. De las Peñas, B. Massuti, R. Blanco, V. Alberola, U. Jimenez, J. R. Delgado, F. Cardenal, M. Tarón, J. L. Ramírez, A. Sanchez, R. Rosell

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

New therapeutic approaches are being developed based on findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) can influence chemosensitivity. The identification of molecular markers, useful for therapeutic decisions in lung cancer, is thus crucial for disease management. The present study evaluated single-nucleotide polymorphisms (SNPs) in XRCC3, XPD and Aurora kinase A in NSCLC patients in order to assess whether these biomarkers were able to predict the outcomes of the patients.

Methods

The Spanish Lung Cancer Group prospectively assessed this clinical study. Eligible patients had histologically confirmed stage IV or IIIB (with malignant pleural effusion) NSCLC, which had not previously been treated with chemotherapy, and a World Health Organization performance status (PS) of 0–1. Patients received intravenous doses of vinorelbine 25 mg/m² on days 1 and 8, and cisplatin 75 mg/m² on day 1, every 21 days for a maximum of 6 cycles. Venous blood was collected from each, and genomic DNA was isolated. SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 were assessed.

Results

The study included 180 patients. Median age was 62 years; 87 % were male; 34 % had PS 0; and 83 % had stage IV disease. The median number of cycles was 4. Time to progression was 5.1 months (95 % CI, 4.2–5.9). Overall median survival was 8.6 months (95 % CI, 7.1–10.1). There was no significant association between SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 in outcome or toxicity.

Conclusions

Our findings indicate that SNPs in XRCC3, XPD or Aurora kinase A cannot predict outcomes in advanced NSCLC patients treated with platinum-based chemotherapy.

Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J et al (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26:3543–3551PubMedCrossRef

Fossella F, Pereira JR, Von Pawel J, Pluzanska A, Gorbounova V et al (2003) Randomized, multinational, phase III study of docetaxel plus platinum combination versus vinorelbine plus cisplatin for advanced non-small cell lung cancer: the TAX 326 study group. J Clin Oncol 21:3016–3024PubMedCrossRef

Gebbia V, Galette D, Caruso M, Verderame F, Pezzella G et al (2008) Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the G.O.I.M. (Gruppo Oncologico Italia Meridionale). Lung Cancer 3:369–377CrossRef

Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2:48–58PubMedCrossRef

van de Vaart PJ, Belderbos J, de Jong D, Sneeuw KC, Majoor D et al (2010) DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy. Int J Cancer 89:160–166

Furuta T, Ueda T, Aune G, Sarasin A, Kraemer KH et al (2002) Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells (2002). Cancer Res 62:4899–4902PubMed

de las Penas R, Sanchez-Ronco M, Alberola V, Taron M, Camps C et al (2006) Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients. Ann Oncol 17:668–675PubMedCrossRef

Aloyz R, Zy Xu, Bello V, Bergeron J, Han FY et al (2002) Regulation of cisplatin resistance and homologous recombinational repair by the TFIIH subunit XPD. Cancer Res 62:5457–5462PubMed

Spitz MR, Wu X, Wang Y, Wang LE, Shete S et al (2001) Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 61:1354–1357PubMed

10.

Gurubhagavatula S, Liu G, Park S, Zhou W, Su L et al (2004) XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 22:2594–2601PubMedCrossRef

11.

Gautschi O, Heigway J, Mack P, Purnell PR, Lara PN et al (2008) Aurora kinases as anticancer drug targets. Clin Cancer Res 14:1639–1648PubMedCrossRef

12.

Lapenna S, Giordano A (2009) Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8:547–566PubMedCrossRef

13.

Mora-Bermudez F, Gerlich D, Ellenberg J (2007) Maximal chromosomes compaction occurs by axial shortening in anaphase and depends on aurora kinase. Nat Cell Biol 9:822–831PubMedCrossRef

14.

Soncini C, Carpinelli P, Gianelli L, Fancelli D, Vianello P et al (2006) PHA-680632 a novel aurora kinase inhibitor with potent antitumoural activity. Clin Cancer Res 12:4080–4089PubMedCrossRef

15.

Wilkinson RW, Odedra R, Heaton SP, Wedge SR, Keen NJ et al (2007) AZD 1152, a selective inhibitor of aurora B kinase, inhibits human xenograft growth by inducing apoptosis. Clin Cancer Res 13:3682–3688PubMedCrossRef

16.

Tong T, Zhong Y, Kong J, Dong L, Song Y et al (2004) Overexpression of Aurora-A contributes to malignant development of human esophageal squamous cell carcinoma. Clin Cancer Res 10(7304):7310 Erratum in: Clin Cancer Res. 2005 Jun 15;11(12):4635

17.

Li D, Zhu J, Firozi PF, Abbruzzese JL, Evans DB et al (2003) Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 9:991–997PubMed

18.

Sakakura C, Hagiwara A, Yasuoka R, Funjita Y, Nakanishi M et al (2001) Tumour amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer 84:824–831PubMedCrossRef

19.

Sen S, Zhou H, Zhang RD, Yoon DS, Vakar-Lopez G et al (2002) Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 94:1320–1329PubMedCrossRef

20.

Miyoshi Y, Iwao K, Egawa C, Noguchi S (2001) Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer 92:370–373PubMedCrossRef

21.

Gritsko TM, Coppola D, Paciga JE, Yang L, Sun M et al (2003) Activation and overexpression of centrosome kinase BTAK/Aurora- A in human ovarian cancer. Clin Cancer Res 9:1420–1426PubMed

22.

Chung CM, Man C, Jin Y, Guan XY, Wang Q et al (2005) Amplification and overexpression of aurora kinaseA (AURKA) in immortalized human ovarian epithelial (HOSE) cells. Mol Carcinog 43:165–174PubMedCrossRef

23.

Tanaka E, Hashimoto Y, Ito T, Okumura T, Kan T et al (2005) The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res 11:1827–1834PubMedCrossRef

24.

25.

Reiter R, Gais P, Jütting U, Steuer-Vogt MK, Pickhard A et al (2006) Aurora kinase A messenger RNA overexpression is correlated with tumour progression and shortened survival in head and neck squamous cell carcinoma. Clin Cancer Res 12:5136–5141PubMedCrossRef

26.

Ruan Y, Song AP, Wang H, Xie YT, Han JY et al (2011) Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population. J Pathol 225:535–543PubMedCrossRef

27.

Sun H, Bai J, Chen F, Jin Y, Yu Y et al (2011) Lack of an association between AURKA T91A polymorphisms and breast cancer: a meta-analysis involving 32,141 subjects. Breast Cancer Res Treat 125:175–179PubMedCrossRef

28.

Liu L, Yuan P, Wu C, Zhang X, Wang F et al (2011) Assessment of XPD Lys751Gln and XRCC1 T-77C polymorphisms in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. Lung Cancer 73:110–115PubMedCrossRef

29.

Wei S-Z, Zhan P, Shi M, Qian Q, Yu L, Song Y (2011) Predictive value of ERCC1 and XPD polymorphism in patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a systematic review and meta-analysis. Med Oncol 28:315–321PubMedCrossRef

30.

Yin M, Yan J, Voutsina J, Tibaldi C, Christiani DC et al (2011) No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: a meta-analysis. Lung Cancer 73:370–377CrossRef

31.

Wei HB, Hu J, Shang LH, Zhang YY, Lu FF et al (2012) A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer. Chin Med J 125:2902–2907PubMed

32.

Yin JY, Huang Q, Zhao YC, Zhou HH, Liu ZQ (2012) Meta-analysis on pharmacogenetics of platinum-based chemotherapy in non small cell lung cancer (NSCLC) patients. PLoS ONE 7:e38150PubMedCrossRef

33.

Giachino DF, Ghio P, Regazzoni S, Mandrile G, Novello S et al (2007) Prospective assessment of XPD Lys751Gln and XDCC1 Arg399Gln single nucleotide polymorphisms in lung cancer. Clin Cancer Res 13:2876–2881PubMedCrossRef

34.

Martoni A, Marino A, Sperandi F, Giaquinta S, Di Fabio F et al (2005) Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer. Eur J Cancer 41:81–92PubMedCrossRef

35.

Georgoulias V, Ardavanis A, Tsiafaki X, Agelidou A, Mixalopoulou P et al (2005) Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol 1:2937–2945CrossRef

36.

Gebbia V, Galetta D, Lorusso V, Caruso M, Verderame F et al (2008) Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the G.O.I.M. (Gruppo Oncologico Italia Meridionale). Lung Cancer 61:369–377PubMedCrossRef

37.

Provencio M, Blanco R, Alberola V, Isla D, Massuti B et al. (2007) Cisplatin plus vinorelbine as first-line treatment for patients with advanced non-small cell lung cancer: molecular correlates. In: 14th European cancer conference, ECCO 14, Barcelona, pp 23–27. September, 2007

38.

Yang H, He L, Kruk P, Nicosia SV, Cheng JQ (2006) Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells. Int J Cancer 119:2304–2312PubMedCrossRef

39.

Anand S, Penrhyn-Lowe S, Venkitaraman AR (2003) AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 3:51–62PubMedCrossRef

40.

Pan JY, Ajani JA, Gu J, Gong Y, Quin A et al (2012) Association of Aurora-A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation. Cancer 118:4346–4353PubMedCrossRef

41.

Viñolas N, Provencio M, Reguart N, Cardenal F, Alberola V et al (2011) Single nucleotide polymorphisms in MDR1 gen correlates with outcome in advanced non-small-cell lung cancer patients treated with cisplatin plus vinorelbine. Lung Cancer 71:191–198PubMedCrossRef

Titel: Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer
verfasst von: M. Provencio
C. Camps
M. Cobo
R. De las Peñas
B. Massuti
R. Blanco
V. Alberola
U. Jimenez
J. R. Delgado
F. Cardenal
M. Tarón
J. L. Ramírez
A. Sanchez
R. Rosell
Publikationsdatum: 01.12.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 6/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1985-9

Springer Medizin

Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer