Frontiers of Medicine in China

, Volume 3, Issue 3, pp 245–255

Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

  • Bo Peng
  • Jinnong Zhang
  • Jamile S. Woods
  • Wei Peng
Review
  • 24 Downloads

Abstract

Lung cancer is one of the most common human cancers and the number one cancer killer in the United States. In general, lung cancer includes small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but NSCLC accounts for approximately 90% of lung cancer. The early diagnosis and therapy of lung cancer still presents a big challenge because validated screening tools, which can improve current early detection to reduce mortality from lung cancer, do not exist. Over the last decade, molecular genetic abnormalities have been described in NSCLC, including chromosomal aberrations, overexpression of oncogenes, and deletion and/or mutations in tumor suppressor genes. These molecular markers in NSCLC demonstrated close associations with the development of lung cancer such as Ras, the epidermal growth factor receptor (EGFR, or c-erbB-1), HER2 (c-erbB-2), c-Met, and Bcl-2. Therefore, this information may be applied for early cancer detection, classification, novel targeted therapy, and prognosis in NSCLC. Recent clinical data have revealed that targeted therapy might be the second-line therapy as an alternative approach. Currently, the targeted therapies are mainly focused on two lung cancer pathways, the EGFR and the vascular endothelial growth factor (VEGF) pathways. Some clinical trials are very encouraging, but some of them are not. However, these trials have not identified a subgroup of NSCLC with biomarkers. Therefore, it is very important to select NSCLC patients with biomarkers to match targeted agents so that we can further identify effectiveness of targeted therapy in the future.

Keywords

lung cancer carcinoma non-small cell lung cancer molecular markers targeted therapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Parkin D M, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin, 2005, 55(2): 74–108PubMedCrossRefGoogle Scholar
  2. 2.
    Alberg A J, Samet J M. Epidemiology of lung cancer. Chest, 2003, 123: 21SPubMedCrossRefGoogle Scholar
  3. 3.
    Zang E A, Wynder E L. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst, 1996, 88(34): 183–192PubMedCrossRefGoogle Scholar
  4. 4.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun M J. Cancer statistics, 2008. CA Cancer J Clin, 2008, 58(2): 71–96PubMedCrossRefGoogle Scholar
  5. 5.
    Molina J R, Adjei A A, Jett J R. Advances in chemotherapy of nonsmall cell lung cancer. Chest, 2006, 130(4): 1211–1219PubMedCrossRefGoogle Scholar
  6. 6.
    Mariadason J M, Augenlicht L H, Arango D. Microarray analysis in the clinical management of cancer. Hematol Oncol Clin North Am, 2003, 17(2): 377–387PubMedCrossRefGoogle Scholar
  7. 7.
    Anglim P P, Alonzo T A, Laird-Offringa I A. DNA methylationbased biomarkers for early detection of non-small cell lung cancer: an update. Mol Cancer, 2008, 7: 81PubMedCrossRefGoogle Scholar
  8. 8.
    Mountain C F. New prognostic factors in lung cancer. Biologic prophets of cancer cell aggression. Chest, 1995, 108(1): 246–254PubMedCrossRefGoogle Scholar
  9. 9.
    Salgia R, Skarin AT. Molecular abnormalities in lung cancer. J Clin Oncol, 1998, 16(3): 1207–1217PubMedGoogle Scholar
  10. 10.
    Strauss GM, Kwiatkowski D J, Harpole D H, Lynch T J, Skarin AT, Sugarbaker D J. Molecular and pathologic markers in stage I nonsmall cell carcinoma of the lung. J Clin Oncol, 1995, 13(5): 1265–1279PubMedGoogle Scholar
  11. 11.
    Rosell R, Felip E, Garcia-Campelo R, Balana C. The biology of nonsmall-cell lung cancer: identifying new targets for rational therapy. Lung Cancer, 2004, 46(2): 135–148PubMedCrossRefGoogle Scholar
  12. 12.
    Devereux T R, Taylor J A, Barrett J C. Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors. Giles F. Filley Lecture. Chest, 1996, 109(3 Suppl): 14S–19SGoogle Scholar
  13. 13.
    Killary A M, Wolf M E, Giambernardi T A, Naylor S L. Definition of a tumor suppressor locus within human chromosome 3p21-p22. Proc Natl Acad Sci USA, 1992, 89(22): 10877–10881PubMedCrossRefGoogle Scholar
  14. 14.
    Otterson G, Lin A, Kay F. Genetic etiology of lung cancer. Oncology (Huntingt), 1992, 6(9): 97–104, 107; discussion 108, 111-112PubMedGoogle Scholar
  15. 15.
    Hirao T, Nelson H H, Ashok T D, Wain J C, Mark E J, Christiani D C,Wiencke J K, Kelsey K T. Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer. Cancer Res, 2001, 61(2): 612–615PubMedGoogle Scholar
  16. 16.
    Hibi, K, Takahashi, T, Yamakawa, K, Ueda R, Sekido Y, Ariyoshi Y, Suyama M, Takagi H, Nakamura Y, Takahashi T. Three distinct regions involved in 3p deletion in human lung cancer. Oncogene, 1992, 7: 445–449PubMedGoogle Scholar
  17. 17.
    Hibi K, Takahashi T, Yamakawa K, Ueda R, Sekido Y, Ariyoshi Y, Suyama M, Takagi H, Nakamura Y, Takahashi T. Deletion mapping of the short arm of chromosome 8 in non-small cell lung carcinoma. Genes Chromosomes Cancer, 1993, 7(3): 85–88Google Scholar
  18. 18.
    Nakachi K, Imai K, Hayashi S, Watanabe J, Kawajiri K. Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res, 1991, 51(19): 5177–5180PubMedGoogle Scholar
  19. 19.
    Ambrosone C B, Rao U, Michalek A M, Cummings K M, Mettlin C J. Lung cancer histologic types and family history of cancer. Analysis of histologic subtypes of 872 patients with primary lung cancer. Cancer, 1993, 72(4): 1192–1198PubMedCrossRefGoogle Scholar
  20. 20.
    Slebos R J, Kibbelaar R E, Dalesio O, Kooistra A, Stam J, Meijer C J, Wagenaar S S, Vanderschueren R G, van Zandwijk N, Mooi W J. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med, 1990, 323(9): 561–565PubMedCrossRefGoogle Scholar
  21. 21.
    Rodenhuis S, Slebos R J. Clinical significance of ras oncogene activation in human lung cancer. Cancer Res, 1992, 52(Suppl): 2665–2669Google Scholar
  22. 22.
    Graziano S L, Gamble G P, Newman N B, Abbott L Z, Rooney M, Mookherjee S, Lamb M L, Kohman L J, Poiesz B J. Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer. J Clin Oncol, 1999, 17(2): 668–675PubMedGoogle Scholar
  23. 23.
    Graziano S L, Gamble G P, Newman N B, Abbott L Z, Rooney M, Mookherjee S, Lamb M L, Kohman L J, Poiesz B J. Cigarette smoking is strongly associated with mutation of the k-ras gene in patients with primary adenocarcinomaof the lung. Cancer, 2001, 92 (6): 1525–1530CrossRefGoogle Scholar
  24. 24.
    Velu T J, Beguinot L, Vass W C, Willingham M C, Merlino G T, Pastan I, Lowy D R. Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. Science, 1987, 238(4832): 1408–1410PubMedCrossRefGoogle Scholar
  25. 25.
    To C T, Tsao M S. The roles of hepatocyte growth factor/scatter factor and met receptor in human cancers (Review). Oncol Rep, 1998, 5(5): 1013–1024PubMedGoogle Scholar
  26. 26.
    Ichimura, E, Maeshima, A, Nakajima, T, Nakamura, T. Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res, 1996, 87(10): 1063–1069PubMedGoogle Scholar
  27. 27.
    Hockenbery D, Nuñez G, Milliman C, Schreiber R D, Korsmeyer S J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 1990, 348(6299): 334–336PubMedCrossRefGoogle Scholar
  28. 28.
    Anton R C, Brown RW, Younes M, Gondo M M, Stephenson M A, Cagle P T. Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: analysis of 427 cases. Hum Pathol, 1997, 28(9): 1079–1082PubMedCrossRefGoogle Scholar
  29. 29.
    Ohmura Y, Aoe M, Andou A, Shimizu N. Telomerase activity and Bcl-2 expression in non-small cell lung cancer. Clin Cancer Res, 2000, 6(8): 2980–2987PubMedGoogle Scholar
  30. 30.
    Laudanski J, Chyczewski L, Niklinska W E, Kretowska M, Furman M, Sawicki B, Niklinski J. Expression of bcl-2 protein in non-small cell lung cancer: correlation with clinicopathology and patient survival. Neoplasma, 1999, 46(1): 25–30PubMedGoogle Scholar
  31. 31.
    Groeger A M, Caputi M, Esposito V, De Luca A, Salat A, Murabito M, Giordano G G, Baldi F, Giordano A, Wolner E. Bcl-2 protein expression correlates with nodal status in non small cell lung cancer. Anticancer Res, 1999, 19(1B): 821–824PubMedGoogle Scholar
  32. 32.
    Pezzella F, Turley H, Kuzu I, Tungekar M F, Dunnill M S, Pierce C B, Harris A, Gatter K C, Mason D Y. bcl-2 protein in non-small cell lung carcinoma. N Engl J Med, 1993, 329(10): 690–694PubMedCrossRefGoogle Scholar
  33. 33.
    Silvestrini R, Costa A, Lequaglie C, Mochen C, Veneroni S, Leutner M, Ravasi G. Bcl-2 protein and prognosis in patients with potentially curable non-small-cell lung cancer. Virchows Arch, 1998, 432(5): 441–444PubMedCrossRefGoogle Scholar
  34. 34.
    Huang C I, Neuberg D, Johnson B E, Wei J Y, Christiani D C. Expression of bcl-2 protein is associated with shorter survival in nonsmall cell lung carcinoma. Cancer, 2003, 98(1): 135–143PubMedCrossRefGoogle Scholar
  35. 35.
    Sharp T V, Munoz F, Bourboulia D, Presneau N, Darai E, Wang H W, Cannon M, Butcher D N, Nicholson A G, Klein G, Imreh S, Boshoff C. LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription. Proc Natl Acad Sci USA, 2004, 101(47): 16531–16536PubMedCrossRefGoogle Scholar
  36. 36.
    Zhang S Y, Liu S C, Johnson D G, Klein-Szanto A J. E2F-1 gene transfer enhances invasiveness of human head and neck carcinoma cell lines. Cancer Res, 2000, 60(21): 5972–5976PubMedGoogle Scholar
  37. 37.
    Banerjee D, Gorlick R, Liefshitz A, Danenberg K, Danenberg P C, Danenberg P V, Klimstra D, Jhanwar S, Cordon-Cardo C, Fong Y, Kemeny N, Bertino J R. Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase. Cancer Res, 2000, 60(9): 2365–2367PubMedGoogle Scholar
  38. 38.
    Lane D P. Cancer. p53, guardian of the genome. Nature, 1992, 358 (6381): 15–16PubMedCrossRefGoogle Scholar
  39. 39.
    Tsao M S, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A, Whitehead M, Zhu C Q, Livingston R, Johnson D H, Rigas J, Seymour L, Winton T, Shepherd F A. Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. J Clin Oncol, 2007, 25(33): 5240–5247PubMedCrossRefGoogle Scholar
  40. 40.
    Knudson A G Jr. The ninth Gordon Hamilton-Fairley memorial lecture. Hereditary cancers: clues to mechanisms of carcinogenesis. Br J Cancer, 1989, 59(5): 661–666PubMedGoogle Scholar
  41. 41.
    Xu H J, Quinlan D C, Davidson A G, Hu S X, Summers C L, Li J, Benedict W F. Altered retinoblastoma protein expression and prognosis in early-stage non-small-cell lung carcinoma. J Natl Cancer Inst, 1994, 86(9): 695–699PubMedCrossRefGoogle Scholar
  42. 42.
    Xu H J, Cagle P T, Hu S X, Li J, Benedict W F. Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis. Clin Cancer Res, 1996, 2(7): 1169–1176PubMedGoogle Scholar
  43. 43.
    Shapiro G I, Rollins B J. p16INK4A as a human tumor suppressor. Biochim Biophys Acta, 1996, 18; 1242(3): 165–169Google Scholar
  44. 44.
    Hannon G J, Beach D. p15INK4B is a potential effector of TGFbeta-induced cell cycle arrest. Nature, 1994, 371(6494): 257–261PubMedCrossRefGoogle Scholar
  45. 45.
    Shapiro G I, Edwards C D, Kobzik L, Godleski J, Richards W, Sugarbaker D J, Rollins B J. Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines. Cancer Res, 1995, 55(3): 505–509PubMedGoogle Scholar
  46. 46.
    Kratzke R A, Greatens T M, Rubins J B, Maddaus M A, Niewoehner D E, Niehans G A, Geradts J. Rb and p16INK4a expression in resected non-small cell lung tumors. Cancer Res, 1996, 56(15): 3415–3420PubMedGoogle Scholar
  47. 47.
    Gonzalez-Quevedo R, Iniesta P, Moran A, de Juan C, Sanchez-Pernaute A, Fernandez C, Torres A, Diaz-Rubio E, Balibrea J L, Benito M. Cooperative role of telomerase activity and p16 expression in the prognosis of non-small-cell lung cancer. J Clin Oncol, 2002, 20(1): 254–262PubMedCrossRefGoogle Scholar
  48. 48.
    Gautam A, Li Z R, Bepler G. RRM1-induced metastasis suppression through PTEN-regulated pathways. Oncogene, 2003, 22(14): 2135–2142PubMedCrossRefGoogle Scholar
  49. 49.
    Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med, 2007, 356(8): 800–808PubMedCrossRefGoogle Scholar
  50. 50.
    Ohta Y, Nozaki Z, Nozawa H, Kamesui T, Tsunezuka Y, Oda M, Watanabe G. The predictive value of vascular endothelial growth factor and nm23 for the diagnosis of occult metastasis in non-small cell lung cancer. Jpn J Cancer Res, 2001, 92(3): 361–366PubMedGoogle Scholar
  51. 51.
    Tomita M, Ayabe T, Matsuzaki Y, Onitsuka T. Immunohistochemical analysis of nm23-H1 gene product in node-positive lung cancer and lymph nodes. Lung Cancer, 1999, 24(1): 11–16PubMedCrossRefGoogle Scholar
  52. 52.
    Higashiyama M, Taki T, Ieki Y, Adachi M, Huang C L, Koh T, Kodama K, Doi O, Miyake M. Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in nonsmall cell lung cancer. Cancer Res, 1995, 55(24): 6040–6044PubMedGoogle Scholar
  53. 53.
    Lau L F, Lam S C. The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res, 1999, 248(1): 44–57PubMedCrossRefGoogle Scholar
  54. 54.
    Chen N, Leu S J, Todorovic V, Lam S C, Lau L F. Identification of a novel integrin alphavbeta3 binding site in CCN1 (CYR61) critical for pro-angiogenic activities in vascular endothelial cells. J Biol Chem, 2004, 279(42): 44166–44176PubMedCrossRefGoogle Scholar
  55. 55.
    Xie D, Yin D, Wang H J, Liu G T, Elashoff R, Black K, Koeffler H P. Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas. Clin Cancer Res, 2004, 10(6): 2072–2081PubMedCrossRefGoogle Scholar
  56. 56.
    Chen C C, Chen N, Lau L F. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem, 2001, 276(13): 10443–10452PubMedCrossRefGoogle Scholar
  57. 57.
    Tong X, Xie D, O’Kelly J, Miller C W, Muller-Tidow C, Koeffler H P. Cyr61, a member of CCN family, is a tumor suppressor in nonsmall cell lung cancer. J Biol Chem, 2001, 276(50): 47709–47714PubMedCrossRefGoogle Scholar
  58. 58.
    Chang C C, Shih J Y, Jeng Y M, Su J L, Lin B Z, Chen S T, Chau Y P, Yang P C, Kuo M L. Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis. J Natl Cancer Inst, 2004, 96(5): 364–375PubMedCrossRefGoogle Scholar
  59. 59.
    Shih J Y, Yang S C, Hong T M, Yuan A, Chen J J, Yu C J, Chang Y L, Lee Y C, Peck K, Wu C W, Yang P C. Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells. J Natl Cancer Inst, 2001, 93(18): 1392–1400PubMedCrossRefGoogle Scholar
  60. 60.
    Pérez-Soler R, Chachoua A, Hammond L A, Rowinsky E K, Huberman M, Karp D, Rigas J, Clark G M, Santabárbara P, Bonomi P. Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol, 2004, 22(16), 3238–3247PubMedCrossRefGoogle Scholar
  61. 61.
    Jackman DM, Yeap B Y, Lindeman N I, Fidias P, Rabin MS, Temel J, Skarin A T, Meyerson M, Holmes A J, Borras A M, Freidlin B, Ostler P A, Lucca J, Lynch T J, Johnson B E, Jänne P A. Phase II clinical trial of chemotherapy-naive patients > or = 70 years of age treated with erlotinib for advanced non-small-cell lung cancer. J Clin Oncol, 2007, 25(7): 760–766PubMedCrossRefGoogle Scholar
  62. 62.
    Shepherd F A, Rodrigues Pereira J, Ciuleanu T, Tan E H, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated nonsmall-cell lung cancer. N Engl J Med, 2005, 353(2): 123–132PubMedCrossRefGoogle Scholar
  63. 63.
    Herbst R S, Prager D, Hermann R, Fehrenbacher L, Johnson B E, Sandler A, Kris MG, Tran H T, Klein P, Li X, Ramies D, Johnson D H, Miller VA; TRIBUTE Investigator Group. TRIBUTE: A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-smallcell lung cancer. J Clin Oncol, 2005, 23(25): 5892–5899PubMedCrossRefGoogle Scholar
  64. 64.
    Gatzemeier U, Pluzanska A, Szczesna A et al. Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and GC chemotherapy in advanced non-small cell lung cancer (NSCLC). J Clin Oncol, 2004, 22(suppl 14): 619sGoogle Scholar
  65. 65.
    Giaccone G, Herbst R S, Manegold C, Scagliotti G, Rosell R, Miller V, Natale R B, Schiller J H, Von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs J S, Averbuch S D, Wolf M K, Rennie P, Fandi A, Johnson D H. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol, 2004, 22(5): 777–784PubMedCrossRefGoogle Scholar
  66. 66.
    Herbst R S, Giaccone G, Schiller J H, Natale R B, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves J A, Wolf M K, Krebs A D, Averbuch S D, Ochs J S, Grous J, Fandi A, Johnson D H. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT 2. J Clin Oncol, 2004, 22(5): 785–794PubMedCrossRefGoogle Scholar
  67. 67.
    Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J Y, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong R P, Baselga J. Multi-institutional randomized Phase II trial of gefitinib for previously treated patients with advanced nonsmall-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol, 2003, 21(12): 2237–2246PubMedCrossRefGoogle Scholar
  68. 68.
    Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan E H, Pemberton K, Archer V, Carroll K. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomized, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet, 2005, 366(6496): 1527–1537PubMedCrossRefGoogle Scholar
  69. 69.
    Hanna N, Lilenbaum R, Ansari R, Lynch T, Govindan R, Jänne PA, Bonomi P. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol, 2006, 24(33): 5253–5258PubMedCrossRefGoogle Scholar
  70. 70.
    Pirker R, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Park K, Gatzemeier U, Bajeta E, Emig M, Pereira J R. A randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CValone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol (Suppl), 2008, 26(15S): 3CrossRefGoogle Scholar
  71. 71.
    Socinski MA. Antibodies to the epidermal growth factor receptor in non-small cell lung cancer: current status of matuzumab and panitumumab. Clinical Cancer Research, 2007, (13): 4597s–4601sCrossRefGoogle Scholar
  72. 72.
    Sandler A, Gray R, Perry M C, Brahmer J, Schiller J H, Dowlati A, Lilenbaum R, Johnson D H. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 2006, 355(24): 2542–2550PubMedCrossRefGoogle Scholar
  73. 73.
    Johnson D H, Fehrenbacher L, Novotny W F, Herbst R S, Nemunaitis J J, Jablons D M, Langer C J, DeVore R F 3rd, Gaudreault J, Damico L A, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol, 2004, 22(11): 2184–2191PubMedCrossRefGoogle Scholar
  74. 74.
    Socinski M A, Novello S, Sanchez J M. Efficacy and safety of sunitinib in previously treated, advanced non-small cell lung cancer (NSCLC): Preliminary results of a multicenter phase II trial. J Clin Oncol, 2006, 24(18S): 7001Google Scholar
  75. 75.
    Tateishi M, Ishida T, Mitsudomi T, Kaneko S, Sugimachi K. Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer, 1991, 27(11): 1372–1375PubMedCrossRefGoogle Scholar
  76. 76.
    Shi D, He G, Cao S, Pan W, Zhang H Z, Yu D, Hung M C. Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. Mol Carcinog, 1992, 5(3): 213–218PubMedCrossRefGoogle Scholar
  77. 77.
    Harpole D H Jr, Herndon J E 2nd, Wolfe W G, Iglehart J D, Marks J R. A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res, 1995, 55(1): 51–56PubMedGoogle Scholar
  78. 78.
    Hsieh C C, Chow K C, Fahn H J, Tsai C M, Li W Y, Huang M H, Wang L S. Prognostic significance of HER-2/neu overexpression in stage I adenocarcinoma of lung. Ann Thorac Surg, 1998, 66(4): 1159–1163PubMedCrossRefGoogle Scholar
  79. 79.
    Cantero R, Torres A J, Maestro M L, Hernando F, Sanz M T, Del Barco V, Gomez A, Fernandez C, Balibrea J L. Prognostic value of the quantified expression of p185 in non-small cell lung cancer. J Thorac Cardiovasc Surg, 2000, 119(6): 1119–1125PubMedCrossRefGoogle Scholar
  80. 80.
    Ardizzoni A, Cafferata MA, Paganuzzi M, Filiberti R, Marroni P, Neri M, Fontana V, Nicolo G, Perdelli L, Stampino C G, Rosso R, Puntoni R. Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma. Cancer, 2001, 92(7): 1896–1904PubMedCrossRefGoogle Scholar
  81. 81.
    Kase S, Sugio K, Yamazaki K, Okamoto T, Yano T, Sugimachi K. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res, 2000, 6 (12): 4789–4796PubMedGoogle Scholar
  82. 82.
    Hommura F, Furuuchi K, Yamazaki K, Ogura S, Kinoshita I, Shimizu M, Moriuchi T, Katoh H, Nishimura M, Dosaka-Akita H. Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas. Cancer, 2002, 94(3): 752–758PubMedCrossRefGoogle Scholar
  83. 83.
    Bremnes R M, Veve R, Gabrielson E, Hirsch F R, Baron A, Bemis L, Gemmill R M, Drabkin H A, Franklin W A. High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol, 2002, 20(10): 2417–2428PubMedCrossRefGoogle Scholar
  84. 84.
    Burbee D G, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar A F, Lerman M I, Zabarovsky E, White M, Minna J D. Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst, 2001, 93(9): 691–699PubMedCrossRefGoogle Scholar
  85. 85.
    Dammann R, Li C, Yoon J H, Chin P L, Bates S, Pfeifer G P. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet, 2000, 25 (3): 315–319PubMedCrossRefGoogle Scholar
  86. 86.
    Maruyama R, Sugio K, Yoshino I, Maehara Y, Gazdar A F. Hypermethylation of FHIT as a prognostic marker in nonsmall cell lung carcinoma. Cancer, 2004, 100(7): 1472–1477PubMedCrossRefGoogle Scholar
  87. 87.
    Huncharek M, Muscat J, Geschwind J F. K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: a combined analysis of 881 cases. Carcinogenesis, 1999, 20: 1507–1510PubMedCrossRefGoogle Scholar
  88. 88.
    Higashiyama M, Kodama K, Yokouchi H, Takami K, Adachi M, Taki T, Ishiguro S, Nakamori S, Yoshie O, Miyake M. KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor: an immunohistochemical analysis. Cancer, 1998, 83(3): 466–474PubMedCrossRefGoogle Scholar
  89. 89.
    Takaoka A, Hinoda Y, Satoh S, Adachi Y, Itoh F, Adachi M, Imai K. Suppression of invasive properties of colon cancer cells by ametastasis suppressor KAI1 gene. Oncogene, 1998, 16(11): 1443–1453PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH 2009

Authors and Affiliations

  • Bo Peng
    • 1
  • Jinnong Zhang
    • 2
  • Jamile S. Woods
    • 3
  • Wei Peng
    • 3
  1. 1.College of Arts and SciencesUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Pulmonary Division of Union HospitalHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of Pulmonary and Critical Care MedicineSalt Lake Regional Medical CenterIasis HealthcareUSA

Personalised recommendations