Advertisement

Clinical and Translational Oncology

, Volume 10, Issue 4, pp 189–197 | Cite as

Genetic changes in small cell lung carcinoma

  • Edurne Arriola
  • Israel Cañadas
  • Montse Arumí
  • Federico Rojo
  • Ana Rovira
  • Joan Albanell
Educational Series

Abstract

Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. Therefore, there is a need to develop novel treatments to improve the outcome of patients with SCLC. To fulfil this need, it is critical to gain further understanding on the molecular basis of SCLC and specifically to identify novel therapeutic targets. Clinical trials with molecularly targeted agents have been performed with little success in the past, but recently many promising oncogenic pathways have been discovered and novel targeted therapies are under evaluation. In this review, we summarise the most relevant genetic and signalling pathway alterations reported to date in SCLC and discuss the potential therapeutic implications of such events.

Keywords

Small cell lung carcinoma Genetic changes Expression profiles Oncogenic pathways 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cooper S, Spiro SG (2006) Small cell lung cancer: treatment review. Respirology 1:241–248.CrossRefGoogle Scholar
  2. 2.
    Govindan R, Page N, Morgensztern D et al (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24:4539–4544PubMedCrossRefGoogle Scholar
  3. 3.
    Cheng S, Evans WK, Stys-Norman D, Shepherd FA (2007) Chemotherapy for relapsed small cell lung cancer: a systematic review and practice guideline. J Thorac Oncol 2:348–354PubMedGoogle Scholar
  4. 4.
    Spira A, Ettinger DS (2004) Multidsciplinary management of lung cancer. N Engl J Med 350:379–392PubMedCrossRefGoogle Scholar
  5. 5.
    Miura I, Graziano SL, Cheng JQ et al (1992) Chromosome alterations in human small cell lung cancer: frequent involvement of 5q. Cancer Res. 52:1322–1328PubMedGoogle Scholar
  6. 6.
    Sozzi G, Bertoglio MG, Borrello MG et al (1987) Chromosomal abnormalities in a primary small cell lung cancer. Cancer Genet Cytogenet 27:45–50PubMedCrossRefGoogle Scholar
  7. 7.
    Testa JR, Graziano SL (1993) Molecular implications of recurrent cytogenetic alterations in human small cell lung cancer. Cancer Detect Prev 17:267–277PubMedGoogle Scholar
  8. 8.
    Testa JR, Liu Z, Feder M et al (1997) Advances in the analysis of chromosome alterations in human lung carcinomas. Cancer Genet Cytogenet 95:20–32PubMedCrossRefGoogle Scholar
  9. 9.
    Naylor SL, Johnson BE, Minna JD, Sakaguchi AY (1987) Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature 329:451–454PubMedCrossRefGoogle Scholar
  10. 10.
    Levin NA, Brzoska PM, Warnock ML et al (1995) Identification of novel regions of altered DNA copy number in small cell lung tumors. Genes Chromosomes Cancer 13:175–185PubMedCrossRefGoogle Scholar
  11. 11.
    Balsara BR, Testa JR (2002) Chromosomal imbalances in human lung cancer. Oncogene 21:6877–6883PubMedCrossRefGoogle Scholar
  12. 12.
    Ried T, Petersen I, Holtgreve-Grez H et al (1994) Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization. Cancer Res 54:1801–1806PubMedGoogle Scholar
  13. 13.
    Brauch H, Johnson B, Hovis J et al (1987) Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung. N Engl J Med 317:1109–1113PubMedGoogle Scholar
  14. 14.
    Kok K, Osinga J, Carritt B et al (1987) Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer. Nature 330:578–581PubMedCrossRefGoogle Scholar
  15. 15.
    Kim YH, Girard L, Giacomini CP et al (2006) Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. Oncogene 25:130–138PubMedCrossRefGoogle Scholar
  16. 16.
    Wistuba II, Gazdar AF, Minna JD (2001) Molecular genetics of small cell lung carcinoma. Semin Oncol 28[Suppl 4]:3–13PubMedCrossRefGoogle Scholar
  17. 17.
    Yokomizo A, Tindall DJ, Drabkin H et al (1998) PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers. Oncogene 17:475–479PubMedCrossRefGoogle Scholar
  18. 18.
    Blackhall FH, Pintilie M, Michael M et al (2003) Expression and prognostic significance of kit, protein kinase B, and mitogen-activated protein kinase in patients with small cell lung cancer. Clin Cancer Res 9:2241–2247PubMedGoogle Scholar
  19. 19.
    Kraus AC, Ferber I, Bachmann SO et al (2002) In vitro chemo-and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene 21:8683–8695PubMedCrossRefGoogle Scholar
  20. 20.
    Mirski SE, Evans CD, Almquist KC et al (1993) Altered topoisomerase II alpha in a drug-resistant small cell lung cancer cell line selected in VP-16. Cancer Res 53:4866–4873PubMedGoogle Scholar
  21. 21.
    Cole SP, Chanda ER, Dicke FP et al (1991) Non-P-glycoprotein-mediated multidrug resistance in a small cell lung cancer cell line: evidence for decreased susceptibility to drug-induced DNA damage and reduced levels of topoisomerase II. Cancer Res 51:3345–3352PubMedGoogle Scholar
  22. 22.
    El-Khoury V, Breuzard G, Fourre N, Dufer J (2007) The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model. Br J Cancer 97:562–573PubMedCrossRefGoogle Scholar
  23. 23.
    Kubo A, Yoshikawa A, Hirashima T et al (1996) Point mutations of the topoisomerase IIalpha gene in patients with small cell lung cancer treated with etoposide. Cancer Res 56:1232–1236PubMedGoogle Scholar
  24. 24.
    Sugita M, Geraci M, Gao B et al (2002) Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma. Cancer Res 62:3971–3979PubMedGoogle Scholar
  25. 25.
    Garber ME, Troyanskaya OG, Schluens K et al (2001) Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci USA 98:13784–13789PubMedCrossRefGoogle Scholar
  26. 26.
    Pedersen N, Mortensen S, Sorensen SB et al (2003) Transcriptional gene expression profiling of small cell lung cancer cells. Cancer Res 63:1943–1953PubMedGoogle Scholar
  27. 27.
    Bhattacharjee A, Richards WG, Staunton J et al (2001) Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98:13790–13795PubMedCrossRefGoogle Scholar
  28. 28.
    Jones MH, Virtanen C, Honjoh D et al (2004) Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles. Lancet 363:775–781PubMedCrossRefGoogle Scholar
  29. 29.
    Virtanen C, Ishikawa Y, Honjoh D et al (2002) Integrated classification of lung tumors and cell lines by expression profiling. Proc Natl Acad Sci USA 99:12357–12362PubMedCrossRefGoogle Scholar
  30. 30.
    Westerman BA, Neijenhuis S, Poutsma A et al (2002) Quantitative reverse transcription-polymerase chain reaction measurement of HASH1 (ASCL1), a marker for small cell lung carcinomas with neuroendocrine features. Clin Cancer Res 8:1082–1086PubMedGoogle Scholar
  31. 31.
    De Smaele E, Fragomeli C, Ferretti E et al (2008) An integrated approach identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated genes in developing cerebellum and medulloblastoma. Neoplasia 10:89–98PubMedCrossRefGoogle Scholar
  32. 32.
    Somasundaram K, Reddy SP, Vinnakota K et al (2005) Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma. Oncogene 24:7073–7083PubMedCrossRefGoogle Scholar
  33. 33.
    Pedersen N, Pedersen MW, Lan MS et al (2006) The insulinoma-associated 1: a novel promoter for targeted cancer gene therapy for small-cell lung cancer. Cancer Gene Ther 13:375–384PubMedCrossRefGoogle Scholar
  34. 34.
    Esquela-Kerscher A, Slack FJ (2006) OncomirsmicroRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRefGoogle Scholar
  35. 35.
    Yanaihara N, Caplen N, Bowman E et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198PubMedCrossRefGoogle Scholar
  36. 36.
    Yu SL, Chen HY, Chang GC et al (2008) MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 13:48–57PubMedCrossRefGoogle Scholar
  37. 37.
    Hayashita Y, Osada H, Tatematsu Y et al (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65:9628–9632PubMedCrossRefGoogle Scholar
  38. 38.
    Angeloni D, ter Elst A, Wei MH et al (2006) Analysis of a new homozygous deletion in the tumor suppressor region at 3p12.3 reveals two novel intronic noncoding RNA genes. Genes Chromosomes Cancer 45:676–691PubMedCrossRefGoogle Scholar
  39. 39.
    ter Elst A, Hiemstra BE, van der Vlies P et al (2006) Functional analysis of lung tumor suppressor activity at 3p21.3. Genes Chromosomes Cancer 45:1077–1093PubMedCrossRefGoogle Scholar
  40. 40.
    Quinn KA, Treston AM, Unsworth EJ et al (1996) Insulin-like growth factor expression in human cancer cell lines. J Biol Chem 271:11477–11483PubMedCrossRefGoogle Scholar
  41. 41.
    Nakanishi Y, Mulshine JL, Kasprzyk PG et al (1988) Insulin-like growth factor-I can mediate autocrine proliferation of human small cell lung cancer cell lines in vitro. J Clin Invest 82:354–359PubMedCrossRefGoogle Scholar
  42. 42.
    Reeve JG, Morgan J, Schwander J, Bleehen NM (1993) Role for membrane and secreted insulin-like growth factor-binding protein-2 in the regulation of insulin-like growth factor action in lung tumors. Cancer Res 53:4680–4685PubMedGoogle Scholar
  43. 43.
    Macaulay VM, Everard MJ, Teale JD et al (1990) Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. Cancer Res 50:2511–2517PubMedGoogle Scholar
  44. 44.
    Warshamana-Greene GS, Litz J, Buchdunger E et al (2005) The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, sensitizes small cell lung cancer cell lines to the effects of chemotherapy. Clin Cancer Res 11:1563–1571PubMedCrossRefGoogle Scholar
  45. 45.
    Warshamana-Greene GS, Litz J, Buchdunger E et al (2004) The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in combination with STI571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling. Mol Cancer Ther 3:527–535PubMedGoogle Scholar
  46. 46.
    Hibi K, Takahashi T, Sekido Y et al (1991) Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer. Oncogene 6:2291–2296PubMedGoogle Scholar
  47. 47.
    Rygaard K, Nakamura T, Spang-Thomsen M (1993) Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts. Br J Cancer 67:37–46PubMedGoogle Scholar
  48. 48.
    Sekido Y, Obata Y, Ueda R et al (1991) Preferential expression of c-kit protooncogene transcripts in small cell lung cancer. Cancer Res 51:2416–2419PubMedGoogle Scholar
  49. 49.
    Jonkers J, Berns A (2004) Oncogene addiction: sometimes a temporary slavery. Cancer Cell 6:535–538PubMedGoogle Scholar
  50. 50.
    Takigawa N, Segawa Y, Fujimoto N et al (1998) Elevated vascular endothelial growth factor levels in sera of patients with lung cancer. Anticancer Res 18:1251–1254PubMedGoogle Scholar
  51. 51.
    Salven P, Ruotsalainen T, Mattson K, Joensuu H (1998) High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer. Int J Cancer 79:144–146PubMedCrossRefGoogle Scholar
  52. 52.
    Fontanini G, Faviana P, Lucchi M et al (2002) A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma. Br J Cancer 86:558–563PubMedCrossRefGoogle Scholar
  53. 53.
    Ruotsalainen T, Joensuu H, Mattson K, Salven P (2002) High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer. Cancer Epidemiol Biomarkers Prev 11:1492–1495PubMedGoogle Scholar
  54. 54.
    Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550PubMedCrossRefGoogle Scholar
  55. 55.
    Litz J, Sakuntala Warshamana-Greene G, Sulanke G et al (2004) The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis, in part by blocking Kit-mediated VEGF expression. Lung Cancer 46:283–291PubMedCrossRefGoogle Scholar
  56. 56.
    Pujol JL, Breton JL, Gervais R et al (2007) Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol 25:3945–3951PubMedCrossRefGoogle Scholar
  57. 57.
    Arnold AM, Seymour L, Smylie M et al (2007) Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20. J Clin Oncol 25:4278–4284PubMedCrossRefGoogle Scholar
  58. 58.
    Okamoto I, Araki J, Suto R et al (2006) EGFR mutation in gefitinib-responsive small-cell lung cancer. Ann Oncol 17:1028–1029PubMedCrossRefGoogle Scholar
  59. 59.
    Zakowski MF, Ladanyi M, Kris MG (2006) EGFR mutations in small-cell lung cancers in patients who have never smoked. N Engl J Med 355:213–215PubMedCrossRefGoogle Scholar
  60. 60.
    Moore AM, Einhorn LH, Estes D et al (2006) Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial. Lung Cancer 52:93–97PubMedCrossRefGoogle Scholar
  61. 61.
    Ma PC, Maulik G, Christensen J, Salgia R (2003) c-Met: structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev 22:309–325PubMedCrossRefGoogle Scholar
  62. 62.
    Maulik G, Kijima T, Ma PC et al (2002) Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res 8:620–627PubMedGoogle Scholar
  63. 63.
    Ma PC, Kijima T, Maulik G et al (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63:6272–6281PubMedGoogle Scholar
  64. 64.
    Ma PC, Jagadeeswaran R, Jagadeesh S et al (2005) Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 65:1479–1488PubMedCrossRefGoogle Scholar
  65. 65.
    Ma PC, Schaefer E, Christensen JG, Salgia R (2005) A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin. Clin Cancer Res 11:2312–2319PubMedCrossRefGoogle Scholar
  66. 66.
    Puri N, Khramtsov A, Ahmed S et al (2007) A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer xenografts. Cancer Res 67:3529–3534PubMedCrossRefGoogle Scholar
  67. 67.
    Shaw RJ, Cantley LC (2006) Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441:424–430PubMedCrossRefGoogle Scholar
  68. 68.
    Albanell J, Dalmases A, Rovira A, Rojo F (2007) mTOR signalling in human cancer. Clin Transl Oncol 9:484–493PubMedCrossRefGoogle Scholar
  69. 69.
    Moore SM, Rintoul RC, Walker TR et al (1998) The presence of a constitutively active phosphoinositide 3-kinase in small cell lung cancer cells mediates anchorage-independent proliferation via a protein kinase B and p70s6k-dependent pathway. Cancer Res 58:5239–5247PubMedGoogle Scholar
  70. 70.
    Razzini G, Berrie CP, Vignati S et al (2000) Novel functional PI 3-kinase antagonists inhibit cell growth and tumorigenicity in human cancer cell lines. FASEB J 14:1179–1187PubMedGoogle Scholar
  71. 71.
    Wu C, Wangpaichitr M, Feun L et al (2005) Overcoming cisplatin resistance by mTOR inhibitor in lung cancer. Mol Cancer 4:25PubMedCrossRefGoogle Scholar
  72. 72.
    Sartorius UA, Krammer PH (2002) Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines. Int J Cancer 97:584–592PubMedCrossRefGoogle Scholar
  73. 73.
    Ikegaki N, Katsumata M, Minna J, Tsujimoto Y (1994) Expression of bcl-2 in small cell lung carcinoma cells. Cancer Res 54:6–8PubMedGoogle Scholar
  74. 74.
    Jiang SX, Sato Y, Kuwao S, Kameya T (1995) Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas. J Pathol 177:135–138PubMedCrossRefGoogle Scholar
  75. 75.
    Ziegler A, Luedke GH, Fabbro D et al (1997) Induction of apoptosis in small-cell lung cancer cells by an antisense oligodeoxynucleotide targeting the Bcl-2 coding sequence. J Natl Cancer Inst 89:1027–1036PubMedCrossRefGoogle Scholar
  76. 76.
    Zangemeister-Wittke U, Schenker T, Luedke GH, Stahel RA (1998) Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines. Br J Cancer 78:1035–1042PubMedGoogle Scholar
  77. 77.
    Rudin CM, Kozloff M, Hoffman PC et al (2004) Phase I study of G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin and etoposide in patients with small-cell lung cancer. J Clin Oncol 22:1110–1117PubMedCrossRefGoogle Scholar
  78. 78.
    Rudin CM, Salgia R, Wang X et al (2008) Randomized phase II Study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103. J Clin Oncol 26:870–876PubMedCrossRefGoogle Scholar
  79. 79.
    Corjay MH, Dobrzanski DJ, Way JM et al (1991) Two distinct bombesin receptor subtypes are expressed and functional in human lung carcinoma cells. J Biol Chem 266:18771–18779PubMedGoogle Scholar
  80. 80.
    Cuttitta F, Carney DN, Mulshine J et al (1985) Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316:823–826PubMedCrossRefGoogle Scholar
  81. 81.
    Martinez A, Zudaire E, Julian M et al (2005) Gastrin-releasing peptide (GRP) induces angiogenesis and the specific GRP blocker 77427 inhibits tumor growth in vitro and in vivo. Oncogene 24:4106–4113PubMedGoogle Scholar
  82. 82.
    Mahmoud S, Staley J, Taylor J et al (1991) [Psi 13,14] bombesin analogues inhibit growth of small cell lung cancer in vitro and in vivo. Cancer Res 51:1798–1802PubMedGoogle Scholar
  83. 83.
    Kelley MJ, Linnoila RI, Avis IL et al (1997) Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer. Chest 112:256–261PubMedCrossRefGoogle Scholar
  84. 84.
    Arriola E, Rodriguez-Pinilla SM, Lambros MB et al (2007) Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer. Breast Cancer Res Treat 106:181–189PubMedCrossRefGoogle Scholar
  85. 85.
    Dingemans AM, Witlox MA, Stallaert RA et al (1999) Expression of DNA topoisomerase IIalpha and topoisomerase IIbeta genes predicts survival and response to chemotherapy in patients with small cell lung cancer. Clin Cancer Res 5:2048–2058PubMedGoogle Scholar
  86. 86.
    Ohe Y, Negoro S, Matsui K et al (2005) Phase I–II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer. Ann Oncol 16:430–436PubMedCrossRefGoogle Scholar
  87. 87.
    Onoda S, Masuda N, Seto T et al (2006) Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 24:5448–5453PubMedCrossRefGoogle Scholar
  88. 88.
    Hanada M, Mizuno S, Fukushima A et al (1998) A new antitumor agent amrubicin induces cell growth inhibition by stabilizing topoisomerase II-DNA complex. Jpn J Cancer Res 89:1229–1238PubMedGoogle Scholar
  89. 89.
    Lanier LL, Testi R, Bindl J, Phillips JH (1989) Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 169:2233–2238PubMedCrossRefGoogle Scholar
  90. 90.
    Doria MI Jr, Montag AG, Franklin WA (1988) Immunophenotype of small cell lung carcinoma. Expression of NKH-1 and transferrin receptor and absence of most myeloid antigens. Cancer 62:1939–1945PubMedCrossRefGoogle Scholar
  91. 91.
    Onuki N, Wistuba II, Travis WD et al (1999) Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 85:600–607PubMedCrossRefGoogle Scholar
  92. 92.
    Nikitina EY, Chada S, Muro-Cacho C et al (2002) An effective immunization and cancer treatment with activated dendritic cells transduced with full-length wild-type p53. Gene Ther 9:345–352PubMedCrossRefGoogle Scholar
  93. 93.
    Antonia SJ, Mirza N, Fricke I et al (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12:878–887PubMedCrossRefGoogle Scholar
  94. 94.
    Cagle PT, el-Naggar AK, Xu HJ et al (1997) Differential retinoblastoma protein expression in neuroendocrine tumors of the lung. Potential diagnostic implications. Am J Pathol 150:393–400PubMedGoogle Scholar
  95. 95.
    Gutova M, Najbauer J, Gevorgyan A et al (2007) Identification of uPAR-positive chemoresistant cells in small cell lung cancer. PLoS ONE 2:e243PubMedCrossRefGoogle Scholar
  96. 96.
    Dammann R, Li C, Yoon JH et al (2000) Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet 25:315–319PubMedCrossRefGoogle Scholar
  97. 97.
    Sozzi G, Veronese ML, Negrini M et al (1996) The FHIT gene 3p14.2 is abnormal in lung cancer. Cell 85:17–26PubMedCrossRefGoogle Scholar
  98. 98.
    Levin NA, Brzoska P, Gupta N et al (1994) Identification of frequent novel genetic alterations in small cell lung carcinoma. Cancer Res 54:5086–5091PubMedGoogle Scholar
  99. 99.
    Brennan J, O’Connor T, Makuch RW et al (1991) myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens. Cancer Res 51:1708–1712PubMedGoogle Scholar
  100. 100.
    Wurster-Hill DH, Cannizzaro LA, Pettengill OS et al (1984) Cytogenetics of small cell carcinoma of the lung. Cancer Genet Cytogenet 13:303–330PubMedCrossRefGoogle Scholar

Copyright information

© Feseo 2008

Authors and Affiliations

  • Edurne Arriola
    • 1
    • 2
  • Israel Cañadas
    • 1
    • 2
  • Montse Arumí
    • 2
    • 3
  • Federico Rojo
    • 2
    • 4
  • Ana Rovira
    • 1
    • 2
  • Joan Albanell
    • 1
    • 2
  1. 1.Medical Oncology ServiceHospital del MarBarcelonaSpain
  2. 2.Cancer Research ProgramIMIM-Hospital del MarBarcelonaSpain
  3. 3.Pathology ServiceHospital del MarBarcelonaSpain
  4. 4.Pathology ServiceFundación Jiménez DíazMadridSpain

Personalised recommendations