About this Journal Submit a Manuscript Table of Contents
ISRN Molecular Biology
Volume 2012 (2012), Article ID 837306, 8 pages
http://dx.doi.org/10.5402/2012/837306
Review Article

K-Ras Mutations in Non-Small-Cell Lung Cancer: Prognostic and Predictive Value

Istituto Toscano Tumori, Ospedale Civile di Livorno, 57100 Livorno, Italy

Received 10 January 2012; Accepted 6 February 2012

Academic Editor: J. S. Castresana

Copyright © 2012 Manolo D’Arcangelo and Federico Cappuzzo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Jemal, R. Siegel, J. Xu, and E. Ward, “Cancer statistics, 2010,” CA Cancer Journal for Clinicians, vol. 60, no. 5, pp. 277–300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. J. H. Schiller, D. Harrington, C. P. Belani et al., “Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer,” New England Journal of Medicine, vol. 346, no. 2, pp. 92–98, 2002. View at Publisher · View at Google Scholar · View at Scopus
  3. G. V. Scagliotti, P. Parikh, J. Von Pawel et al., “Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 26, no. 21, pp. 3543–3551, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Reck, J. Von Pawel, P. Zatloukal et al., “Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAiL,” Journal of Clinical Oncology, vol. 27, no. 8, pp. 1227–1234, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. I. B. Weinstein, “Cancer: addiction to oncogenes—the Achilles heal of cancer,” Science, vol. 297, no. 5578, pp. 63–64, 2002. View at Publisher · View at Google Scholar · View at Scopus
  6. G. H. Fisher, S. L. Wellen, D. Klimstra et al., “Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes,” Genes and Development, vol. 15, no. 24, pp. 3249–3262, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. T. S. Mok, Y. L. Wu, S. Thongprasert et al., “Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma,” New England Journal of Medicine, vol. 361, no. 10, pp. 947–957, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. J. S. Lee, K. Park, S.-W. Kim, et al., “A randomized phase III study of gefitinib (IRESSA) versus standard chemotherapy (gemcitabine plus cisplatin) as a first-line treatment for never-smokers with advanced or metastatic adenocarcinoma of the lung,” Journal of Thoracic Oncology, vol. 4, supplement 19, abstract PRS 4, 2009.
  9. T. Mitsudomi, S. Morita, Y. Yatabe et al., “Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial,” The Lancet Oncology, vol. 11, no. 2, pp. 121–128, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Maemondo, A. Inoue, K. Kobayashi et al., “Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR,” New England Journal of Medicine, vol. 362, no. 25, pp. 2380–2388, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Zhou, Y.-L. Wu, G. Chen, et al., “Efficay results from the randomised phase II OPTIMAL (CTNOG 0802) study comparing first-line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM), in chinese advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR activating mutation,” Annals of Oncology, vol. 21, supplement 8, abstract LBA 13, 2010.
  12. C.-H. Yang, M. Fukuoka, T. S. Mok, et al., “Finall overall survival (OS) results from a phase III, randomised, open-label, first-line study of gefitinib (G) v carboplatin/paclitaxel (C/P) in clinically selected patients with advanced non-small-cell lung cancer (NSCLC) in Asia (IPASS),” Annals of Oncology, vol. 21, supplement 8, abstract LBA 2, 2010.
  13. F. A. Shepherd, J. R. Pereira, T. Ciuleanu et al., “Erlotinib in previously treated non-small-cell lung cancer,” New England Journal of Medicine, vol. 353, no. 2, pp. 123–132, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. F. Cappuzzo, T. Ciuleanu, L. Stelmakh et al., “Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study,” The Lancet Oncology, vol. 11, no. 6, pp. 521–529, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. V. A. Miller, P. O'Connor, C. Soh, and F. Kabbinavar, “A randomized, double-blind, placebo-controlled, phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC),” Journal of Clinical Oncology, vol. 27, supplement 18, abstract LBA8002, 2009.
  16. E. S. Kim, V. Hirsh, T. Mok et al., “Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial,” The Lancet, vol. 372, no. 9652, pp. 1809–1818, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Ciuleanu, L. Stelmakh, S. Cicenas, et al., “Efficacy and safety of erlotinib versus chemotherapy in second-line advanced non small cell lung cancer (NSCLC) with poor prognosis: the phase III TITAN study,” Lung Cancer, vol. 71, no. 2, supplement, pp. S44–S47, 2011.
  18. C. J. Allegra, J. M. Jessup, M. R. Somerfield et al., “American society of clinical oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy,” Journal of Clinical Oncology, vol. 27, no. 12, pp. 2091–2096, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. J. L. Bos, “Ras oncogenes in human cancer: a review,” Cancer Research, vol. 49, no. 17, pp. 4682–4689, 1989. View at Scopus
  20. S. Rodenhuis, M. L. Van de Wetering, and W. J. Mooi, “Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung,” New England Journal of Medicine, vol. 317, no. 15, pp. 929–935, 1987. View at Scopus
  21. A. Jemal, R. Siegel, E. Ward et al., “Cancer statistics, 2008,” CA Cancer Journal for Clinicians, vol. 58, no. 2, pp. 71–96, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Forbes, J. Clements, E. Dawson et al., “Cosmic 2005,” British Journal of Cancer, vol. 94, no. 2, pp. 318–322, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. G. J. Riely, M. G. Kris, J. L. Marks, et al., “Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma,” Journal of Clinical Oncology, vol. 26, supplement 15, abstract 8006, 2008.
  24. M. S. Tsao, S. Aviel-Ronen, K. Ding et al., “Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 25, no. 33, pp. 5240–5247, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. J. H. Schiller, S. Adak, R. H. Feins et al., “Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a laboratory ancillary study on an eastern cooperative oncology group prospective randomized trial of postoperative adjuvant therapy,” Journal of Clinical Oncology, vol. 19, no. 2, pp. 448–457, 2001. View at Scopus
  26. S. L. Graziano, G. P. Gamble, N. B. Newman et al., “Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 17, no. 2, pp. 668–675, 1999. View at Scopus
  27. P. Keohavong, M. A. A. DeMichele, A. C. Melacrinos, R. J. Landreneau, R. J. Weyant, and J. M. Siegfried, “Detection of K-ras mutations in lung carcinomas: relationship to prognosis,” Clinical Cancer Research, vol. 2, no. 2, pp. 411–418, 1996. View at Scopus
  28. C. Lu, J. C. Soria, X. Tang et al., “Prognostic factors in resected stage I non-small-cell lung cancer: a multivariate analysis of six molecular markers,” Journal of Clinical Oncology, vol. 22, no. 22, pp. 4575–4583, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. R. J. C. Slebos, R. E. Kibbelaar, O. Dalesio et al., “K-Ras oncogene activation as a prognostic marker in adenocarcinoma of the lung,” New England Journal of Medicine, vol. 323, no. 9, pp. 561–565, 1990. View at Scopus
  30. H. H. Nelson, D. C. Christiani, E. J. Mark, J. K. Wiencke, J. C. Wain, and K. T. Kelsey, “Implications and prognostic value of K-ras mutation for early-stage lung cancer in women,” Journal of the National Cancer Institute, vol. 91, no. 23, pp. 2032–2038, 1999. View at Scopus
  31. Y. Fukuyama, T. Mitsudomi, K. Sugio, T. Ishida, K. Akazawa, and K. Sugimachi, “K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small-cell lung cancer,” British Journal of Cancer, vol. 75, no. 8, pp. 1125–1130, 1997. View at Scopus
  32. C. L. Huang, T. Taki, M. Adachi et al., “Mutations of p53 and K-ras genes as prognostic factors for non-small cell lung cancer,” International Journal of Oncology, vol. 12, no. 3, pp. 553–563, 1998. View at Scopus
  33. M. Miyake, M. Adachi, C. L. Huang, M. Higashiyama, K. Kodama, and T. Taki, “A novel molecular staging protocol for non-small cell lung cancer,” Oncogene, vol. 18, no. 14, pp. 2397–2404, 1999. View at Scopus
  34. J. L. Marks, S. Broderick, Q. Zhou et al., “Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma,” Journal of Thoracic Oncology, vol. 3, no. 2, pp. 111–116, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Mascaux, N. Iannino, B. Martin et al., “The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis,” British Journal of Cancer, vol. 92, no. 1, pp. 131–139, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. T. Winton, R. Livingston, D. Johnson et al., “Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer,” New England Journal of Medicine, vol. 352, no. 25, pp. 2589–2597, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. M. S. Tsao, P. Hainaut, A. Bourredjem, et al., “LACE-bio pooled analysis of the prognostic and predictive value of KRAS mutation in completely resected non-small cell lung cancer (NSCLC),” Annals of Oncology, vol. 21, supplement 8, abstract 4218, 2010.
  38. C. Camps, E. Jantus-Lewintre, A. Cabrera et al., “The identification of KRAS mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non-small cell lung cancer patients,” Lung Cancer, vol. 72, pp. 365–369, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Kalikaki, A. Koutsopoulos, D. Hatzidaki et al., “Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status,” Lung Cancer, vol. 69, no. 1, pp. 110–115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. G. Giaccone, M. G. Ruiz, T. Le Chevalier et al., “Erlotinib for frontline treatment of advanced non-small cell lung cancer: a phase II study,” Clinical Cancer Research, vol. 12, no. 20, pp. 6049–6055, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. D. M. Jackman, B. Y. Yeap, N. I. Lindeman et al., “Phase II clinical trial of chemotherapy-naïve patients ≥ 70 years of age treated with erlotinib for advanced non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 25, no. 7, pp. 760–766, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. W. Pao, T. Y. Wang, G. J. Riely et al., “KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib,” PLoS Medicine, vol. 2, no. 1, pp. 0057–0061, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. E. Massarelli, M. Varella-Garcia, X. Tang et al., “KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer,” Clinical Cancer Research, vol. 13, no. 10, pp. 2890–2896, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Linardou, I. J. Dahabreh, D. Kanaloupiti et al., “Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer,” The Lancet Oncology, vol. 9, no. 10, pp. 962–972, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. C. Mao, L. X. Qiu, R. Y. Liao et al., “KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: a meta-analysis of 22 studies,” Lung Cancer, vol. 69, no. 3, pp. 272–278, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. D. A. Eberhard, B. E. Johnson, L. C. Amler et al., “Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib,” Journal of Clinical Oncology, vol. 23, no. 25, pp. 5900–5909, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Q. Zhu, G. Da Cunha Santos, K. Ding et al., “Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada clinical trials group study BR.21,” Journal of Clinical Oncology, vol. 26, no. 26, pp. 4268–4275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. W. Brugger, N. Triller, M. Blasinska-Morawiec et al., “Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 29, no. 31, pp. 4113–4120, 2011. View at Publisher · View at Google Scholar
  49. J. Y. Douillard, F. A. Shepherd, V. Hirsh et al., “Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial,” Journal of Clinical Oncology, vol. 28, no. 5, pp. 744–752, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. R. Pirker, J. R. Pereira, A. Szczesna et al., “Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial,” The Lancet, vol. 373, no. 9674, pp. 1525–1531, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. T. J. Lynch, T. Patel, L. Dreisbach et al., “Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099,” Journal of Clinical Oncology, vol. 28, no. 6, pp. 911–917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. R. Pirker, J. R. Pereira, J. Von Pawel et al., “EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study,” The Lancet Oncology, vol. 13, no. 1, pp. 33–42, 2012. View at Publisher · View at Google Scholar
  53. F. Di Fiore, F. Blanchard, F. Charbonnier et al., “Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy,” British Journal of Cancer, vol. 96, no. 8, pp. 1166–1169, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Khambata-Ford, C. R. Garrett, N. J. Meropol et al., “Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab,” Journal of Clinical Oncology, vol. 25, no. 22, pp. 3230–3237, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Lièvre, J.-B. Bachet, V. Boige et al., “KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab,” Journal of Clinical Oncology, vol. 26, no. 3, pp. 374–379, 2008. View at Publisher · View at Google Scholar
  56. S. Khambata-Ford, C. T. Harbison, L. L. Hart et al., “Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer,” Journal of Clinical Oncology, vol. 28, no. 6, pp. 918–927, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. K. J. O'Byrne, U. Gatzemeier, I. Bondarenko et al., “Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study,” The Lancet Oncology, vol. 12, no. 8, pp. 795–805, 2011. View at Publisher · View at Google Scholar
  58. K. D. Danenberg, P. P. Grimminger, P. C. Mack, et al., “KRAS mutations (MTs) in non-small cell lung cancer (NSCLC) versus colorectal cancer (CRC): implications for cetuximab therapy,” ASCO Meeting Abstracts, vol. 28, no. 15, abstract 10529, 2010.
  59. L. Sequist, W. Akerley, W. Brugger, D. Ferrari, E. Garmey, and D. Gerber, “Final results from ARQ197-209: a global randomized placebo-controlled phase 2 clinical trial of erlotinib plus ARQ197 versus erlotinib plus placebo in previously treated EGFR-inhibitor naive patients with advanced non-small cell lung cancer (NSCLC),” Annals of Oncology, vol. 21, supplement 8, abstract viii122, 2010.
  60. T. Maurer, L. Garrenton, A. Oh, et al., “Drugging the undraggable: small-molecule inhibition of the Ras oncoprotein,” Molecular Biology of the Cell, vol. 22, supplement, Abstract 24, 2011.