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Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer

Oncogene volume 22, pages 3548–3553 (2003)Cite this article

Abstract

Non-small-cell lung cancer patients with locally advanced or metastatic disease at the time of diagnosis show marginal response to chemotherapy in terms of tumor shrinkage, time to progression and median survival. The identification and implementation of predictive genetic markers of response-specific cytotoxic drugs is a priority of current research and future trials. In this study, we have used quantitative PCR to analyse expression of β-tubulin III, stathmin, RRM1, COX-2 and GSTP1 in mRNA isolated from paraffin-embedded tumor biopsies of 75 nonsmall-cell lung cancer patients treated as part of a large randomized trial. In total, 22 patients were treated with gemcitabine/cisplatin, 25 with vinorelbine/cisplatin and 28 with paclitaxel/carboplatin. There were no differences in clinical characteristics and transcript levels in the pretreatment biopsies according to treatment arm. Patients with low β-tubulin III levels had better response in the paclitaxel/carboplatin arm (P=0.05), and those with low RRM1 levels showed a tendency to better response in the gemcitabine/cisplatin arm. Time to progression was influenced by β-tubulin III (P=0.03) and stathmin (P=0.05) levels in the vinorelbine/cisplatin arm, and there was a tendency toward correlation between β-tubulin III levels and time to progression in the paclitaxel/carboplatin arm. RRM1 levels influenced time to progression (P=0.05) and even more so, survival (P=0.0028) in the gemcitabine/cisplatin arm. The predictive value of β-tubulin III, stathmin and RRM1 should be tested in prospective customized chemotherapy trials, the results of which will help tailor chemotherapy to improve patient survival.

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References

  • Amayed P, Pantaloni D and Carlier MF . (2002). J. Biol. Chem., 277, 22718–22724.

  • Bepler G, O'Briant KC, Kim YCh, Schreiber G and Pitterle DM . (1999). Genomics, 55, 164–175.

  • Bepler G, Gautam A, McIntyre LM, Beck AF, Chervinsky DS, Kim Y-CH, Pitterle DM and Hyland Y . (2002). J. Clin. Oncol., 20, 1353–1360.

  • Blagosklonny MV and Fojo T . (1999). Int. J. Cancer, 83, 151–156.

  • Bol DK, Rowley RB, Ho CP, Pilz B, Dell J, Swerdel M, Kiguchi K, Muga S, Klein R and Fischer SM . (2002). Cancer Res., 62, 2516–2521.

  • Bonomi P, Kim KM, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M and Johnson D . (2000). J. Clin. Oncol., 18, 623–631.

  • Brattsand G . (2000). Br. J. Cancer, 83, 311–318.

  • Cardenal F, López-Cabrerizo M P, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba J L, Nguyen B, Altai A and Rosell R . (1999). J. Clin. Oncol., 17, 12–18.

  • Crinò L, Scagliotti G, Marangolo M, Figoli F, Clerici M, DeMarinis F, Salvati F, Cruciani G, Dogliotti L, Pucci F, Paccagnella A, Adamo V, Altavilla G, Incoronato P, Trippetti M, Mosconi AM, Santucci A, Sorbolini S, Oliva C and Tonato M . (1997). J. Clin. Oncol., 15, 297–303.

  • Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravioli A, Adamo V, Portalone L, Cruciani G, Massoti A, Ferrara G, Gozzelino F and Tonato M . (1999). J. Clin. Oncol., 17, 3522–3530.

  • Giannakakou P, Gussio R, Nogales E, Downing KH, Zaharevitz D, Bollbuck B, Poy G, Sackett D, Nicolaou KC and Tojo T . (2000a). Proc. Natl. Acad. Sci. USA, 97, 2904–2909.

  • Giannakakou P, Poy G, Zhan Z, Knutsen T, Blagosklonny MV and Fojo T . (2000b). Oncogene, 19, 3078–3085.

  • Giannakakou P, Sackett DL, Kang Y-K, Zhan Z, Buters JTM, Fojo T and Poruchynsky MS . (1997). J. Biol. Chem., 272, 17118–17125.

  • Gibson UE, Heid CA and Wiliams PM . (1996). Genome Res., 6, 995–1001.

  • Goan YG, Zhou B, Hu E, Mi S and Yen Y . (1999). Cancer Res., 59, 4204–4207.

  • Goto S, Yoshida K, Morikawa T, Urata Y, Suzuki K and Kondo T . (1995). Cancer Res., 55, 4297–4301.

  • Harbottle A . (2002). The Cancer Handbook, Alison MR (ed). Nature Publishing Group Macmillan Publishers Ltd: London, pp. 1347–1358.

    Google Scholar 

  • He L, Yang C-PH and Horwitz SB . (2001). Mol. Cancer Ther., 1, 3–10.

  • Heid CA, Stevens J, Livak KJ and Williams PM . (1996). Genome Res., 6, 986–994.

  • Iancu C, Mistry SJ, Arkin S and Atweh GF . (2000). Cancer Res., 60, 3537–3541.

  • Iwata T, Namikawa K, Honma M, Mori N, Yachiku S and Kiyama H . (2002). Mol. Brain Res., 102, 105–109.

  • Kavallaris M, Burkhart CA and Horwitz SB . (1999). Br. J. Cancer, 80, 1020–1025.

  • Kavallaris M, Kuo DY-S, Burkhart CA, Regl DL, Norris MD and Haber M . (1997). J. Clin. Invest., 100, 1282–1293.

  • Kelley MJ, Li S and Harpole DH . (2001). J. Natl. Cancer Inst., 93, 1886–1888.

  • Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffie P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P and Tursz T . (1994). J. Clin. Oncol., 12, 360–367.

  • Li M, Wu X and Xu XC . (2001). Int. J. Cancer, 93, 218–223.

  • Lord RV, Salonga D, Danenberg KD, Peters JH, DeMeester TR, Park JM, Johansson J, Skinner KA, Chandrasoma P, DeMeester SR, Bremner CG, Tsai PI and Danenberg PV . (2000). J. Gastrointest. Surg., 4, 135–142.

  • Lord RVN, Brabender J, Gandara D, Alberola V, Camps C, Domine M, Cardenal F, Sanchez JM, Gumerlock PH, Taron M, Sanchez JJ, Danenberg KD, Danenberg PV and Rosell R . (2002) Clin. Cancer Res., 8, 2286–2291.

  • Monzo M, Rosell R, Sanchez JJ, Lee JS, O'Brate A, Gonzalez-Larriba JL, Alberola V, Lorenzo JC, Nuñez L, Ro JY and Martin C . (1999). J. Clin. Oncol., 17, 1786–1793.

  • Monzo M, Taron M and Rosell R . (2002). J. Natl. Cancer Inst., 94, 61–62.

  • Nicoletti MI, Valoti G, Giannakakou P, Zhan Z, Kim J-H, Lucchini V, Landoni F, Mayo JG, Giavazzi R and Fojo T . (2001). Clin. Cancer Res., 7, 2912–2922.

  • Nishio K, Nakamura T, Koh Y, Kanzawa F, Tamura T and Saijo N . (2001). Cancer, 91, 1494–1499.

  • Pitterle DM, Kim Y-Ch, Jolicoeur EMC, Cao Y, O'Briant KC and Bepler G . (1999). Mamm. Genome, 10, 916–922.

  • Ramsey SD, Moinpour CM, Lovat LC, Crowley JJ, Grevstad P, Presant CA, Rivkin SE, Kelly K and Gandara DR . (2002). J. Natl. Cancer Inst., 94, 291–297.

  • Ranganathan S, Benetatos CA, Colarusso PJ, Dexter DW and Hudes GR . (1998). Br. J. Cancer, 77, 562–566.

  • Š ale S, Sung R, Shen P, Yu K, Wang Y, Duran GE, Kim J-H, Fojo T, Oefner PJ and Sikic BI . (2002). Mol. Cancer Ther., 1, 215–225.

  • Sandler AB, Nemunaitis J, Denham C, Von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold CH, Palmer MC, Gregor A, Nguyen B, Niyikiza C and Einhorn LH . (2000). J. Clin. Oncol., 18, 122–130.

  • Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, Bianco A, Boni C, Marangolo M, Failla G, Adamo V, Altavilla G, Ceribelli A, Clerici M, Di Costanzo F, Frontini L and Tonato M . (2001). Proc. Am. Soc. Clin. Oncol., 20, 308a (abstract 1227).

  • Song S and Xu XC . (2001). Biochem. Biophys. Res. Commun., 281, 872–877.

  • Tsurutani J, Komiya T, Uejima H, Tada H, Syunichi N, Oka M, Kohno S, Fukuoka M and Nakagawa K . (2002). Lung Cancer, 35, 11–16.

  • Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, Albain KS, Kelly K, Taylor SA, Gandara DR and Livingstone RB . (1998). J. Clin. Oncol., 16, 2459–2465.

  • Zhao B and Bepler G . (2001). Oncogene, 20, 8154–8164.

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Acknowledgements

This research was supported in part by a grant from the Spanish Ministry of Health (FIS 00/0445) and by Eli Lilly and Company, Indianapolis, IN, USA. The authors thank Renee O'Brate, Beatriz Rodrigo and Lourdes Franquet for their invaluable help. We are indebted to Dr Paraskevi Giannakakou, Emory Cancer Center, Atlanta, and to Dr David Gandara and Dr Paul Gumerlock, UC Davis Cancer Center, Sacramento, USA for their generous and constructive advice.

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Authors and Affiliations

  1. Department of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    Rafael Rosell & Miquel Taron

  2. Department of Clinical & Biological Sciences, University of Turin, Turin, Italy

    Giorgio Scagliotti & Silvia Novello

  3. Response Genetics, Los Angeles, 90033, CA, USA

    Kathleen D Danenberg, Reginald VN Lord, Janine Cooc, Dennis Salonga & Craig Stephens

  4. Thoracic Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, 33612, FL, USA

    Gerold Bepler

  5. Department of Oncology, Bellaria Hospital, Bologna, Italy

    Lucio Crinò

  6. Autonomous University, Madrid, Spain

    José Javier Sánchez

  7. Department of Oncology, Santa Maria Nuova Hospital, Reggio Emilia, Italy

    Corrado Boni

  8. Department of Oncology, Forlanini Hospital, Rome, Italy

    Filippo De Marinis

  9. Policlinico Hospital, Perugia, Italy

    Maurizio Tonato

  10. Santa Maria delle Croci Hospital, Ravenna, Italy

    Maurizio Marangolo

  11. Infermi Hospital, Biella, Italy

    Felice Gozzelino

  12. S. Maria Hospital Terni, Italy

    Franceso Di Costanzo

  13. Department of Oncology, Regina Elena Institute, Rome, Italy

    Massimo Rinaldi

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  1. Rafael Rosell
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Correspondence to Rafael Rosell.

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Rosell, R., Scagliotti, G., Danenberg, K. et al. Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small-cell lung cancer. Oncogene 22, 3548–3553 (2003). https://doi.org/10.1038/sj.onc.1206419

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