A translational view of the molecular pathogenesis of lung cancer

Journal of Thoracic Oncology

Volumn 2, Issue 4, 2007, Pages 327-343

  Sato, Mitsuo ^a   Shames, David S ^a,b   Gazdar, Adi F ^b   Minna, John D ^a,b,c  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Clinic; Early detection; Epidermal growth factor receptor; Lung cancer; Molecular pathogenesis; Prevention; Targeted therapy; Tyrosine kinase inhibitor

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; ADVEXIN; ANTINEOPLASTIC AGENT; AP 23576; AZACITIDINE; CETUXIMAB; CYCLIN D1; CYCLIN DEPENDENT KINASE 4; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; EVEROLIMUS; GEFITINIB; IMATINIB; LOPERAMIDE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MYC PROTEIN; PD 03255901; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN P16INK4A; PROTEIN P53; PROTEIN TYROSINE KINASE INHIBITOR; RAF PROTEIN; RAPAMYCIN; RAS PROTEIN; SORAFENIB; STAT PROTEIN; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; DNA;

ANGIOGENESIS; APOPTOSIS; CANCER CHEMOTHERAPY; CANCER GENE THERAPY; CANCER IMMUNOTHERAPY; CANCER RESEARCH; CANCER SUSCEPTIBILITY; CELL IMMORTALIZATION; DIARRHEA; ENZYME ACTIVATION; GENE AMPLIFICATION; GENE MUTATION; GENE OVEREXPRESSION; GENOMIC INSTABILITY; HUMAN; IMMUNE RESPONSE; INTERSTITIAL LUNG DISEASE; LUNG CANCER; LUNG NON SMALL CELL CANCER; MELANOMA; MICROARRAY ANALYSIS; MONOTHERAPY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN TARGETING; PROTO ONCOGENE; RASH; REVIEW; SIGNAL TRANSDUCTION; SMOKING; CELL TRANSFORMATION; DNA METHYLATION; EARLY DIAGNOSIS; FEMALE; GENETIC PREDISPOSITION; GENETICS; GENOMICS; LUNG TUMOR; MALE; MASS SCREENING; METABOLISM; METHODOLOGY; MOLECULAR BIOLOGY; PATHOPHYSIOLOGY; PREVALENCE; PROGNOSIS; RISK FACTOR; SMALL CELL CARCINOMA; SURVIVAL; TUMOR SUPPRESSOR GENE; UNITED STATES;

CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, SMALL CELL; CELL TRANSFORMATION, NEOPLASTIC; DNA METHYLATION; DNA, NEOPLASM; EARLY DIAGNOSIS; FEMALE; GENES, TUMOR SUPPRESSOR; GENETIC PREDISPOSITION TO DISEASE; GENOMICS; HUMANS; LUNG NEOPLASMS; MALE; MASS SCREENING; MOLECULAR BIOLOGY; PREVALENCE; PROGNOSIS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RISK FACTORS; SMOKING; SURVIVAL ANALYSIS; UNITED STATES;

EID: 34247891719     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1097/01.JTO.0000263718.69320.4c     Document Type: Article

References (187)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106-130.
2. Shopland DR. Tobacco use and its contribution to early cancer mortality with a special emphasis on cigarette smoking. Environ Health Perspect 1995;103(Suppl 8):131-142.
3. Bach PB, Kelley MJ, Tate RC, McCrory DC. Screening for lung cancer: a review of the current literature. Chest 2003;123:72S-82S.
4. Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763-1771.
5. Belinsky SA, Liechty KC, Gentry FD, et al. Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res 2006;66:3338-3344.
6. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ 1995;311:899-909.
7. Sekido Y, Fong KM, Minna JD. Molecular genetics of lung cancer. Annu Rev Med 2003;54:73-87.
8. Wistuba, II, Behrens C, Virmani AK, et al. High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res 2000;60:1949-1960.
9. Sandler AB, Gray R, Brahmer J,et al. Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC # 704865) in patients with advanced non-squamous non-small cell lung cancer (NSCLC): an Eastern Cooperative Oncology Group (ECOG) trial - E4599. Pro Am Soc Clin Onc 2005;23:16S (abstract 14).
10. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-2139.
11. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-1500.
12. Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 2003;3:733-744.
13. Hecht SS. Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 1999;91:1194-1210.
14. Amos CI, Xu W, Spitz MR. Is there a genetic basis for lung cancer susceptibility? Recent Results Cancer Res 1999;151:3-12.
15. Caporaso NE. Why have we failed to find the low penetrance genetic constituents of common cancers? Cancer Epidemiol Biomarkers Prev 2002;11:1544-1549.
16. Paz-Elizur T, Krupsky M, Blumenstein S, Elinger D, Schechtman E, Livneh Z. DNA repair activity for oxidative damage and risk of lung cancer. J Natl Cancer Inst 2003;95:1312-1319.
17. Bailey-Wilson JE, Amos CI, Pinney SM, et al. A major lung cancer susceptibility locus maps to chromosome 6q23-25. Am J Hum Genet 2004;75:460-474.
18. Smith LT, Lin M, Brena RM, et al. Epigenetic regulation of the tumor suppressor gene TCF21 on 6q23-q24 in lung and head and neck cancer. Proc Natl Acad Sci U S A 2006;103:982-987.
19. Lengauer C Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998;396:643-649.
20. Cahill DP, Lengauer C, Yu J, et al. Mutations of mitotic checkpoint genes in human cancers. Nature 1998;392:300-303.
21. Sato M, Sekido Y, Horio Y, et al. Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. Jpn J Cancer Res 2000;91:504-509.
22. Michel LS Liberal V, Chatterjee A, et al. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 2001;409:355-359.
23. Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998;58:5248-5257.
24. Adachi J, Shiseki M, Okazaki T, et al. Microsatellite instability in primary and metastatic lung carcinomas. Genes Chromosomes Cancer 1995;14:301-306.
25. Chen XQ, Stroun M, Magnenat JL, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med 1996;2:1033-1035.
26. Peltomaki P, Lothe RA, Aaltonen LA, et al. Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome. Cancer Res 1993;53:5853-5855.
27. Rosell R, Pifarre A, Monzo M, et al. Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors. Int J Cancer 1997;74:330-334.
28. Sozzi G, Musso K, Ratcliffe C, Goldstraw P, Pierotti MA, Pastorino U. Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis. Clin Cancer Res 1999;5:2689-2692.
29. Weinstein IB. Cancer. Addiction to oncogenes - the Achilles heal of cancer. Science 2002;297:63-64.
30. Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004;305:1163-1167.
31. Rowinsky EK. The erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors. Annu Rev Med 2004;55:433-457.
32. Franklin WA, Veve R, Hirsch FR, Helfrich BA, Bunn JrPA Epidermal growth factor receptor family in lung cancer and premalignancy. Semin Oncol 2002;29:3-14.
33. Shigematsu H, Gazdar AF. Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer 2006;118:257-262.
34. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005;97:339-346.
35. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (the IDEAL 1 trial) [corrected]. J Clin Oncol 2003;21:2237-2246.
36. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290:2149-2158.
37. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005;353:123-132.
38. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005;353:133-144.
39. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306-13311.
40. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-792.
41. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73.
42. Inukai M, Toyooka S, Ito S, et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 2006;66:7854-7858.
43. Bell DW, Gore I, Okimoto RA, et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005;37:1315-1316.
44. Kobayashi S, Ji H, Yuza Y, et al. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res 2005;65:7096-7101.
45. Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 2005;97:643-655.
46. Cappuzzo F, Magrini E, Ceresoli GL, et al. Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 2004;96:1133-1141.
47. Cappuzzo F, Toschi L, Domenichini I, et al. HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients. Br J Cancer 2005;93:1334-1340.
48. Cappuzzo F, Varella-Garcia M, Shigematsu H, et al. Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients. J Clin Oncol 2005;23:5007-5018.
49. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17.
50. Cappuzzo F, Gregorc V, Rossi E, et al. Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. J Clin Oncol 2003;21:2658-2663.
51. Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005;23:8081-8092.
52. Eberhard DA, Johnson BE, Amler LC, 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. J Clin Oncol 2005;23:5900-5909.
53. Mitsudomi T, Kosaka T, Endoh H, et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 2005;23:2513-2520.
54. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005;366:1527-1537.
55. Barlesi F, Jacot W, Astoul P, Pujol JL. Second-line treatment for advanced non-small cell lung cancer: a systematic review. Lung Cancer 2006;51:159-172.
56. Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 1. J Clin Oncol 2004;22:777-784.
57. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 2. J Clin Oncol 2004;22:785-794.
58. Perez-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 2005;23:5235-5246.
59. Kato T, Nishio K. Clinical aspects of epidermal growth factor receptor inhibitors: benefit and risk. Respirology 2006;11:693-698.
60. Sandler AB. Nondermatologic adverse events associated with anti-EGFR therapy. Oncology (Williston Park) 2006;20:35-40.
61. Ando M, Okamoto I, Yamamoto N, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2006;24:2549-2556.
62. Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005;65:1642-1646.
63. Stephens P, Hunter C, Bignell G, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004;431:525-526.
64. Soung YH, Lee JW, Kim SY, et al. Somatic mutations of the ERBB4 kinase domain in human cancers. Int J Cancer 2006;118:1426-1429.
65. Tang X, Shigematsu H, Bekele BN, et al. EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res 2005;65:7568-7572.
66. Ji H, Li D, Chen L, et al. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell 2006;9:485-495.
67. Politi K, Zakowski MF, Fan PD, Schonfeld EA, Pao W, Varmus HE. Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes Dev 2006;20:1496-1510.
68. Das AK, Sato M, Story MD, et al. Non-small cell lung cancers with kinase domain mutations in the epidermal growth factor receptor are sensitive to ionizing radiation. Cancer Res 2006;66:9601-9608.
69. Sekido Y, Obata Y, Ueda R, et al. Preferential expression of c-kit protooncogene transcripts in small cell lung cancer. Cancer Res 1991;51:2416-2419.
70. Boldrini L, Ursino S, Gisfredi S, et al. Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res 2004;10:4101-4108.
71. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-580.
72. Wang WL, Healy ME, Sattler M, et al. Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571. Oncogene 2000;19:3521-3528.
73. Johnson BE, Fischer T, Fischer B, et al. Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res 2003;9:5880-5887.
74. Krug LM, Crapanzano JP, Azzoli CG, et al. Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer 2005;103:2128-2131.
75. Wolff NC, Randle DE, Egorin MJ, Minna JD, Ilaria RL Imatinib mesylate efficiently achieves therapeutic intratumor concentrations in vivo but has limited activity in a xenograft model of small cell lung cancer. Clin Cancer Res 2004;10:3528-3534.
76. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003;3:11-22.
77. Stacey DW, Kung HF. Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein. Nature 1984;310:508-511.
78. Isobe T, Herbst RS, Onn A. Current management of advanced non-small cell lung cancer: targeted therapy. Semin Oncol 2005;32:315-328.
79. Brose MS, Volpe P, Feldman M, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002;62:6997-7000.
80. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-954.
81. Naoki K, Chen TH, Richards WG, Sugarbaker DJ, Meyerson M. Missense mutations of the BRAF gene in human lung adenocarcinoma. Cancer Res 2002;62:7001-7003.
82. Liu B, Barrett T, Choyke P, et al. A phase II study of BAY 43-9006 (Sorafenib) in patients with relapsed non-small cell lung cancer (NSCLC). Pro Am Soc Clin Onc 2005;24:18S (abstract 17119).
83. Tuveson DA, Weber BL, Herlyn M. BRAF as a potential therapeutic target in melanoma and other malignancies. Cancer Cell 2003;4:95-98.
84. Hoshino R, Chatani Y, Yamori T, et al. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 1999;18:813-822.
85. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501.
86. Kawano O, Sasaki H, Endo K, et al. PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer 2006;54:209-215.
87. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
88. Brognard J, Clark AS, Ni Y, Dennis PA. Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res 2001;61:3986-3997.
89. Forgacs E, Biesterveld EJ, Sekido Y, et al. Mutation analysis of the PTEN/MMAC1 gene in lung cancer. Oncogene 1998;17:1557-1565.
90. Marsit CJ, Zheng S, Aldape K, et al. PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration. Hum Pathol 2005;36:768-776.
91. Gomez-Martin C, Rubio-Viqueira B, Hidalgo M. Current status of mammalian target of rapamycin inhibitors in lung cancer. Clin Lung Cancer 2005;7(Suppl 1):S13-S18.
92. Darnell JrJE STATs and gene regulation. Science 1997;277:1630-1635.
93. Alvarez JV, Greulich H, Sellers WR, Meyerson M, Frank DA. Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor. Cancer Res 2006;66:3162-3168.
94. Song L, Turkson J, Karras JG, Jove R, Haura EB. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene 2003;22:4150-4165.
95. Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 2005;6:635-645.
96. Richardson GE, Johnson BE. The biology of lung cancer. Semin Oncol 1993;20:105-127.
97. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer 2002;2:594-604.
98. Hainaut P, Hernandez T, Robinson A, et al. IARC database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualisation tools. Nucleic Acids Res 1998;26:205-213.
99. Takahashi T, Nau MM, Chiba I, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 1989;246:491-494.
100. Jackson EL, Olive KP, Tuveson DA, et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res 2005;65:10280-10288.
101. van Oijen MG, Slootweg PJ. Gain-of-function mutations in the tumor suppressor gene p53. Clin Cancer Res 2000;6:2138-2145.
102. Takahashi T, Carbone D, Takahashi T, et al. Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res 1992;52:2340-2343.
103. Roth JA, Nguyen D, Lawrence DD, et al. Retrovirus-mediated wildtype p53 gene transfer to tumors of patients with lung cancer. Nat Med 1996;2:985-991.
104. Gabrilovich DI. INGN 201 (Advexin): adenoviral p53 gene therapy for cancer. Expert Opin Biol Ther 2006;6:823-832.
105. Merten OW, Geny-Fiamma C, Douar AM. Current issues in adeno-associated viral vector production. Gene Ther 2005;12(Suppl 1):S51-S61.
106. Higashiyama M, Doi O, Kodama K, et al. MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Br J Cancer 1997;75:1302-1308.
107. Gazzeri S, Della Valle V, Chaussade L, Brambilla C, Larsen CJ, Brambilla E. The human p19ARF protein encoded by the beta transcript of the p16INK4a gene is frequently lost in small cell lung cancer. Cancer Res 1998;58:3926-3931.
108. Vonlanthen S, Heighway J, Tschan MP, et al. Expression of p16INK4a/p16alpha and p19ARF/p16beta is frequently altered in non-small cell lung cancer and correlates with p53 overexpression. Oncogene 1998;17:2779-2785.
109. Friend SH, Bernards R, Rogelj S, et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986;323:643-646.
110. Sherr CJ, McCormick F. The RB and p53 pathways in cancer. Cancer Cell 2002;2:103-112.
111. Reissmann PT, Koga H, Takahashi R, et al. Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer. The Lung Cancer Study Group. Oncogene 1993;8:1913-1919.
112. Shimizu E, Coxon A, Otterson GA, et al. RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma. Oncogene 1994;9:2441-2448.
113. Wikman H, Nymark P, Vayrynen A, et al. CDK4 is a probable target gene in a novel amplicon at 12q13.3-q14.1 in lung cancer. Genes Chromosomes Cancer 2005;42:193-199.
114. Zhao X, Weir BA, LaFramboise T, et al. Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis. Cancer Res 2005;65:5561-5570.
115. Betticher DC, Heighway J, Hasleton PS, et al. Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. Br J Cancer 1996;73:294-300.
116. Ratschiller D, Heighway J, Gugger M, et al. Cyclin D1 overexpression in bronchial epithelia of patients with lung cancer is associated with smoking and predicts survival. J Clin Oncol 2003;21:2085-2093.
117. Elliott RL, Blobe GC. Role of transforming growth factor beta in human cancer. J Clin Oncol 2005;23:2078-2093.
118. de Jonge RR, Garrigue-Antar L, Vellucci VF, Reiss M. Frequent inactivation of the transforming growth factor beta type II receptor in small-cell lung carcinoma cells. Oncol Res 1997;9:89-98.
119. Nagatake M, Takagi Y, Osada H, et al. Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers. Cancer Res 1996;56:2718-2720.
120. Uchida K, Nagatake M, Osada H, et al. Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cancer Res 1996;56:5583-5585.
121. Lerman MI, Minna JD. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res 2000;60:6116-6133.
122. Burbee DG, Forgacs E, Zochbauer-Muller S, et al. Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst 2001;93:691-699.
123. Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet 2000;25:315-319.
124. Agathanggelou A, Cooper WN, Latif F. Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Cancer Res 2005;65:3497-3508.
125. Zabarovsky ER, Lerman MI, Minna JD. Chromosome 3 abnormalities in lung cancer. In: Pass HI, Carbone DP, Johnson DH, Minna JD, Turrisi AT, Eds. Lung cancer: principles and practice. Philadelphia, PA: Lippincott Williams & Wilkins, 2005:118-134.
126. Kondo M, Ji L, Kamibayashi C, et al. Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells. Oncogene 2001;20:6258-6262.
127. Ji L, Nishizaki M, Gao B, et al. Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo. Cancer Res 2002;62:2715-2720.
128. Ito I, Ji L, Tanaka F, et al. Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo. Cancer Gene Ther 2004;11:733-739.
129. Nakamura F, Kalb RG, Strittmatter SM. Molecular basis of semaphorin-mediated axon guidance. J Neurobiol 2000;44:219-229.
130. Sekido Y, Bader S, Latif F, et al. Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. Proc Natl Acad Sci U S A 1996;93:4120-4125.
131. Castro-Rivera E, Ran S, Thorpe P, Minna JD. Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci U S A 2004;101:11432-11437.
132. Tomizawa Y, Sekido Y, Kondo M, et al. Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci U S A 2001;98:13954-13959.
133. Kusy S, Nasarre P, Chan D, et al. Selective suppression of in vivo tumorigenicity by semaphorin SEMA3F in lung cancer cells. Neoplasia 2005;7:457-465.
134. Sozzi G, Veronese ML, Negrini M, et al. The FHIT gene 3p14.2 is abnormal in lung cancer. Cell 1996;85:17-26.
135. Sozzi G, Tornielli S, Tagliabue E, et al. Absence of Fhit protein in primary lung tumors and cell lines with FHIT gene abnormalities. Cancer Res 1997;57:5207-5212.
136. Sard L, Accornero P, Tornielli S, et al. The tumor-suppressor gene FHIT is involved in the regulation of apoptosis and in cell cycle control. Proc Natl Acad Sci U S A 1999;96:8489-8492.
137. Virmani AK, Rathi A, Zochbauer-Muller S, et al. Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. J Natl Cancer Inst 2000;92:1303-1307.
138. Houle B, Rochette-Egly C, Bradley WE. Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells. Proc Natl Acad Sci U S A 1993;90:985-989.
139. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002;3:415-428.
140. Tsou JA, Hagen JA, Carpenter CL, Laird-Offringa IA. DNA methylation analysis: a powerful new tool for lung cancer diagnosis. Oncogene 2002;21:5450-5461.
141. Zochbauer-Muller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD. Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res 2001;61:249-255.
142. Palmisano WA, Divine KK, Saccomanno G, et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 2000;60:5954-5958.
143. Shames DS, Girard L, Gao B, et al. A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med 2006;3:e486.
144. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429-2440.
145. Hu Y, Bebb G, Tan S, et al. Antitumor efficacy of oblimersen Bcl-2 antisense oligonucleotide alone and in combination with vinorelbine in xenograft models of human non-small cell lung cancer. Clin Cancer Res 2004;10:7662-7670.
146. Herbst RS, Frankel SR. Oblimersen sodium (Genasense bcl-2 antisense oligonucleotide): a rational therapeutic to enhance apoptosis in therapy of lung cancer. Clin Cancer Res 2004;10:4245s-4248s.
147. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005;435:677-681.
148. Yin C, Knudson CM, Korsmeyer SJ, Van Dyke T. Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 1997;385:637-640.
149. Brambilla E, Negoescu A, Gazzeri S, et al. Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol 1996;149:1941-1952.
150. Shay JW, Wright WE. Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 2006;5:577-584.
151. Meyerson M. Role of telomerase in normal and cancer cells. J Clin Oncol 2000;18:2626-2634.
152. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70.
153. Hiyama K, Hiyama E, Ishioka S, et al. Telomerase activity in small-cell and non-small-cell lung cancers. J Natl Cancer Inst 1995;87:895-902.
154. Dikmen ZG, Gellert GC, Jackson S, et al. In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res 2005;65:7866-7873.
155. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990;82:4-6.
156. Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet 1992;340:145-146.
157. O'Byrne KJ, Koukourakis MI, Giatromanolaki A, et al. Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer. Br J Cancer 2000;82:1427-1432.
158. Heymach JV, Johnson BE, Rowbottom JA, et al. A randomized, placebo-controlled phase II trial of ZD6474 plus docetaxel, in patients with NSCLC. Pro Am Soc Clin Oncol 2005;23:16S (abstract 3023).
159. Korkolopoulou P, Kaklamanis L, Pezzella F, Harris AL, Gatter KC. Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. Br J Cancer 1996;73:148-153.
160. Niehans GA, Brunner T, Frizelle SP, et al. Human lung carcinomas express Fas ligand. Cancer Res 1997;57:1007-1012.
161. Nemunaitis J, Sterman D, Jablons D, et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 2004;96:326-331.
162. Blattman JN, Greenberg PD. Cancer immunotherapy: a treatment for the masses. Science 2004;305:200-205.
163. Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314:126-129.
164. Balsara BR, Testa JR. Chromosomal imbalances in human lung cancer. Oncogene 2002;21:6877-6883.
165. Coe BP, Lockwood WW, Girard L, et al. Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer. Br J Cancer 2006;94:1927-1935.
166. Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF, Minna JD. Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res 2000;60:4894-4906.
167. Testa JR, Liu Z, Feder M, et al. Advances in the analysis of chromosome alterations in human lung carcinomas. Cancer Genet Cytogenet 1997;95:20-32.
168. Tonon G, Wong KK, Maulik G, et al. High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A 2005;102:9625-9630.
169. Meyerson M, Franklin WA, Kelley MJ. Molecular classification and molecular genetics of human lung cancers. Semin Oncol 2004;31:4-19.
170. Hayes DN, Monti S, Parmigiani G, et al. Gene expression profiling reveals reproducible human lung adenocarcinoma subtypes in multiple independent patient cohorts. J Clin Oncol 2006;24:5079-5090.
171. Potti A, Mukherjee S, Petersen R, et al. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006;355:570-580.
172. Kikuchi T, Daigo Y, Katagiri T, et al. Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs. Oncogene 2003;22:2192-2205.
173. Bild AH, Yao G, Chang JT, et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 2006;439:353-357.
174. Spira A, Beane J, Shah V, et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101:10143-10148.
175. Shah V, Sridhar S, Beane J, Brody JS, Spira A. SIEGE: Smoking Induced Epithelial Gene Expression Database. Nucleic Acids Res 2005;33:D573-D579.
176. Meuwissen R, Berns A. Mouse models for human lung cancer. Genes Dev 2005;19:643-664.
177. Olive KP, Tuveson DA, Ruhe ZC, et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 2004;119:847-860.
178. Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 2003;4:181-189.
179. Ramirez RD, Sheridan S, Girard L, et al. Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res 2004;64:9027-9034.
180. Sato M, Vaughan MB, Girard L, et al. Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Cancer Res 2006;66:2116-2128.
181. Vaughan MB, Ramirez RD, Wright WE, Minna JD, Shay JW. A three-dimensional model of differentiation of immortalized human bronchial epithelial cells. Differentiation 2006;74:141-148.
182. Bjerkvig R, Tysnes BB, Aboody KS, Najbauer J, Terzis AJ. Opinion: the origin of the cancer stem cell: current controversies and new insights. Nat Rev Cancer 2005;5:899-904.
183. Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a
184. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645-648.
185. Al-Hajj M, Wicha MS, Benito-Hernandez Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100:3983-3988.
186. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396-401.
187. Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005;121:823-835.