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Impact of Genetic Targets on Cancer Therapy pp 385–404Cite as

Small-Cell Lung Cancer: An Update on Targeted Therapies

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Part of the book series: Advances in Experimental Medicine and Biology ((volume 779))

Abstract

Lung cancer is the leading cause of cancer-related deaths world-wide and small-cell lung cancer (SCLC) accounts for up to 25% of lung cancer deaths. There has been a considerable amount of research in the understanding of the depth of biology of SCLC and utilizing this knowledge to develop targeted approaches. The treatment of SCLC remains a challenge, despite remarkable initial efficacy to combination chemotherapy and radiation therapy. The response is usually short-lived and the prognosis of SCLC has not changed over the past few decades, necessitating the critical need for evaluating novel agents/therapies. Several signaling pathways have been found to be activated in SCLC tumor cells, forming a rationale for blocking some of the drugable targets. Molecular changes and biological markers have been identified but remain to be validated. Novel and targeted agents have been evaluated but without much success. Increasing understanding of the biology and potential clinical evaluation of biomarkers will pave the way for more effective treatments.

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References

  1. Society AC. Cancer facts and figures 2007. Atlanta: American Cancer Society; 2007.

    Google Scholar 

  2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.

    Article  PubMed  Google Scholar 

  3. Navada S, Lai P, Schwartz AG, Kalemkerian GP. Temporal trends in small cell lung cancer: analysis of the national Surveillance, Epidemiology, and End-Results (SEER) database. J Clin Oncol. 2006;24:7082. 2006 ASCO Annual Meeting Proceedings Part I. 2006, (June 20 Supplement).

    Google Scholar 

  4. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. 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. 2006;24(28):4539–44.

    Article  PubMed  Google Scholar 

  5. Kelly K. Treatment of extensive stage small cell lung cancer. Cancer Treat Res. 2001;105:253–76.

    Article  PubMed  CAS  Google Scholar 

  6. Thatcher N, Eckardt J, Green M. Options for first- and second-line therapy in small cell lung cancer—a workshop discussion. Lung Cancer. 2003;41(Suppl 4):S37–41.

    Article  PubMed  Google Scholar 

  7. Chiappori AA, Rocha-Lima CM. New agents in the treatment of small-cell lung cancer: focus on gemcitabine. Clin Lung Cancer. 2003;4(Suppl 2):S56–63.

    Article  PubMed  Google Scholar 

  8. Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol. 1997;15(5):2090–6.

    PubMed  CAS  Google Scholar 

  9. Wistuba II, Behrens C, Virmani AK, Mele G, Milchgrub S, Girard L, 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(7):1949–60.

    PubMed  CAS  Google Scholar 

  10. Tammemagi MC, McLaughlin JR, Bull SB. Meta-analyses of p53 tumor suppressor gene alterations and clinicopathological features in resected lung cancers. Cancer Epidemiol Biomarkers Prev. 1999;8(7):625–34.

    PubMed  CAS  Google Scholar 

  11. Hainaut P, Hernandez T, Robinson A, Rodriguez-Tome P, Flores T, Hollstein M, 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(1):205–13.

    Article  PubMed  CAS  Google Scholar 

  12. Casey G, Lopez ME, Ramos JC, Plummer SJ, Arboleda MJ, Shaughnessy M, et al. DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known p53 alterations in human malignancies. Oncogene. 1996;13(9):1971–81.

    PubMed  CAS  Google Scholar 

  13. 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(3):315–9.

    Article  PubMed  CAS  Google Scholar 

  14. Richardson GE, Johnson BE. The biology of lung cancer. Semin Oncol. 1993;20(2):105–27.

    PubMed  CAS  Google Scholar 

  15. Kitada S, Takayama S, De Riel K, Tanaka S, Reed JC. Reversal of chemoresistance of lymphoma cells by antisense-mediated reduction of bcl-2 gene expression. Antisense Res Dev. 1994;4(2):71–9.

    PubMed  CAS  Google Scholar 

  16. Ewen ME. The cell cycle and the retinoblastoma protein family. Cancer Metastasis Rev. 1994;13(1):45–66.

    Article  PubMed  CAS  Google Scholar 

  17. Wistuba II, Gazdar AF, Minna JD. Molecular genetics of small cell lung carcinoma. Semin Oncol. 2001;28(2 Suppl 4):3–13.

    Article  PubMed  CAS  Google Scholar 

  18. Ma PC, Tretiakova MS, Nallasura V, Jagadeeswaran R, Husain AN, Salgia R. Downstream signalling and specific inhibition of c-MET/HGF pathway in small cell lung cancer: implications for tumour invasion. Br J Cancer. 2007;97(3):368–77.

    Article  PubMed  CAS  Google Scholar 

  19. Rygaard K, Nakamura T, Spang-Thomsen M. 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. 1993;67(1):37–46.

    Article  PubMed  CAS  Google Scholar 

  20. Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 2003;63(19):6272–81.

    PubMed  CAS  Google Scholar 

  21. Bharti A, Ma PC, Maulik G, Singh R, Khan E, Skarin AT, et al. Haptoglobin alpha-subunit and hepatocyte growth factor can potentially serve as serum tumor biomarkers in small cell lung cancer. Anticancer Res. 2004;24(2C):1031–8.

    PubMed  CAS  Google Scholar 

  22. Wójcik E, Jakubowicz J, Skotnicki P, Sas-Korczyńska B, Kulpa JK. IL-6 and VEGF in small cell lung cancer patients. Anticancer Res. 2010;30(5):1773–8.

    PubMed  Google Scholar 

  23. Damstrup L, Rygaard K, Spang-Thomsen M, Poulsen HS. Expression of the epidermal growth factor receptor in human small cell lung cancer cell lines. Cancer Res. 1992;52(11):3089–93.

    PubMed  CAS  Google Scholar 

  24. Yabu T, Tomimoto H, Taguchi Y, Yamaoka S, Igarashi Y, Okazaki T. Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate. Blood. 2005;106(1):125–34.

    Article  PubMed  CAS  Google Scholar 

  25. Pujol JL, Breton JL, Gervais R, Tanguy M-L, Quoix E, David P, et al. 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. 2007;25(25):3945–51.

    Article  PubMed  CAS  Google Scholar 

  26. Lee SM, Woll PJ, Rudd R, Ferry D, O’Brien M, Middleton G, et al. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009;101(15):1049–57.

    Article  PubMed  CAS  Google Scholar 

  27. Patton JF, Spigel DR, Greco FA, Liggett WH, Zubkus JD, Baskette M, et al. Irinotecan (I), carboplatin (C), and radiotherapy (RT) followed by maintenance bevacizumab (B) in the treatment (tx) of limited-stage small cell lung cancer (LS-SCLC): update of a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2006;24(18S):7085. 2006 ASCO Annual Meeting Proceedings Part I. 2006, (June 20 Supplement).

    Google Scholar 

  28. Genentech Letter: Important drug warning regarding Avastin (bevacizumab). http://www.gene.com/gene/products/information/pdf/avastin_te_letter.pdf, April, 2007.

  29. Ready NE, Dudek AZ, Pang HH, Hodgson LD, Graziano SL, Green MR, et al. Cisplatin, irinotecan, and bevacizumab for untreated extensive-stage small-cell lung cancer: CALGB 30306, a phase II study. J Clin Oncol. 2011;29(33):4436–41.

    Article  PubMed  CAS  Google Scholar 

  30. Sandler A, Szwaric S, Dowlati A, Moore DF, Schiller JH. A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): A trial of the Eastern Cooperative Oncology Group. J Clin Oncol (Meeting Abstracts) June 2007, 25(18_suppl), 7564

    Google Scholar 

  31. Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29(16):2215–22.

    Article  PubMed  CAS  Google Scholar 

  32. Herbst RS, Onn A, Sandler A. Angiogenesis and lung cancer: prognostic and therapeutic implications. J Clin Oncol. 2005;23(14):3243–56.

    Article  PubMed  CAS  Google Scholar 

  33. Gitlitz BJ, Glisson BS, Moon J, Reimers H, Gandara DR. Sorafenib in patients with platinum (plat) treated extensive stage small cell lung cancer (E-SCLC): A SWOG (S0435) phase II trial. ASCO annual meeting 2008. J Clin Oncol 26: 2008 (May 20 suppl; abstr 8039).

    Google Scholar 

  34. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005;65(10):4389–400.

    Article  PubMed  CAS  Google Scholar 

  35. Ramalingam SS, Belani CP, Mack PC, Vokes EE, Longmate J, Govindan R, et al. Phase II study of Cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (National Cancer Institute #7097). J Thorac Oncol. 2010;5(8):1279–84.

    Article  PubMed  Google Scholar 

  36. Arnold AM, Seymour L, Smylie M, Ding K, Ung Y, Findlay B, et al. 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. 2007;25(27):4278–84.

    Article  PubMed  CAS  Google Scholar 

  37. Eichholz A, Merchant S, Gaya AM. Anti-angiogenesis therapies: their potential in cancer management. Onco Targets Ther. 2010;3:69–82.

    PubMed  CAS  Google Scholar 

  38. Potti A, Moazzam N, Ramar K, Hanekom DS, Kargas S, Koch M. CD117 (c-KIT) overexpression in patients with extensive-stage small-cell lung carcinoma. Ann Oncol. 2003;14(6):894–7.

    Article  PubMed  CAS  Google Scholar 

  39. Johnson BE, Fischer T, Fischer B, Dunlop D, Rischin D, Silberman S, et al. Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res. 2003;9(16 Pt 1):5880–7.

    PubMed  CAS  Google Scholar 

  40. Krug LM, Crapanzano JP, Azzoli CG, Miller VA, Rizvi N, Gomez J, et al. Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer. 2005;103(10):2128–31.

    Article  PubMed  CAS  Google Scholar 

  41. Schneider BJ, Gadgeel S, Ramnath N, Worden FP, Wozniak A, Ruckdeschel J, et al. Phase II trial of imatinib maintenance therapy after irinotecan and cisplatin in patients with c-kit positive extensive-stage small cell lung cancer J Clin Oncol (Meeting Abstracts) June 2006 24(18_suppl 17089). 2006.

    Google Scholar 

  42. Spigel DR, Hainsworth JD, Simons L, Meng C, Burris 3rd HA, Yardley DA, et al. Irinotecan, carboplatin, and imatinib in untreated extensive-stage small-cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network. J Thorac Oncol. 2007;2(9):854–61.

    Article  PubMed  Google Scholar 

  43. Glisson BS. Targeting an autocrine loop in small-cell lung cancer: irrelevant target or ­ineffective drug? Clin Lung Cancer. 2010;11(4):222. © 2010 other.

    Article  PubMed  Google Scholar 

  44. Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, et al. SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC. J Clin Oncol. 2009;27(15 s,):suppl; abstr 8001.

    Google Scholar 

  45. Tatematsu A, Shimizu J, Murakami Y, Horio Y, Nakamura S, Hida T, et al. Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res. 2008;14(19):6092–6.

    Article  PubMed  CAS  Google Scholar 

  46. Moore AM, Einhorn LH, Estes D, Govindan R, Axelson J, Vinson J, et al. Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial. Lung Cancer. 2006;52(1):93–7.

    Article  PubMed  CAS  Google Scholar 

  47. Maulik G, Kijima T, Ma PC, Ghosh SK, Lin J, Shapiro GI, et al. Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res. 2002;8(2):620–7.

    PubMed  CAS  Google Scholar 

  48. Bonnie S, Glisson M. First-line therapy of small-cell lung cancer with platinum-based chemotherapy plus AMG 479 or AMG 102. Commun Oncol. 2009;6(suppl 1):1–4. © 2009 Elsevier Inc.

    Google Scholar 

  49. NCT00791154-A Phase 1b/2 Trial of AMG 479 or AMG 102 in combination with platinum-based chemotherapy as first-line treatment for extensive stage small cell lung cancer. www.clinicaltrials.gov.

  50. Arcaro A, Khanzada UK, Vanhaesebroeck B, Tetley TD, Waterfield MD, Seckl MJ. Two distinct phosphoinositide 3-kinases mediate polypeptide growth factor-stimulated PKB activation. EMBO J. 2002;21(19):5097–108. doi:10.1093/emboj/cdf512.

    Article  PubMed  CAS  Google Scholar 

  51. Marin M, Algirdas Z, Pardo OE, et al. AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001. Clin Cancer Res. 2009;15(4):1227–86.

    Google Scholar 

  52. Tarhini A, Kotsakis A, Gooding W, Shuai Y, Petro D, Friedland D, et al. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clin Cancer Res. 2010;16(23):5900–7.

    Article  PubMed  CAS  Google Scholar 

  53. Owonikoko TK, Stoller RG, Petro D, Flaugh R, Hershberger PA, Belani CP, et al. Phase II study of RAD001 (Everolimus) in previously treated small cell lung cancer (SCLC). J Clin Oncol (Meeting Abstracts). May 2008;26(15_suppl 19017).

    Google Scholar 

  54. Pandya KJ, Dahlberg S, Hidalgo M, Cohen RB, Lee MW, Schiller JH, et al. A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). J Thorac Oncol. 2007;2(11):1036–41.

    Article  PubMed  Google Scholar 

  55. Kulik G, Klippel A, Weber MJ. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol. 1997;17(3):1595–606.

    PubMed  CAS  Google Scholar 

  56. Warshamana-Greene GS, Litz J, Buchdunger E, Hofmann F, Garcia-Echeverria C, Krystal GW. 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. 2004;3(5):527–35.

    PubMed  CAS  Google Scholar 

  57. Miller AA, Pang H, Hodgson L, Ramnath N, Otterson GA, Kelley MJ, et al. A phase II study of dasatinib in patients with chemosensitive relapsed small cell lung cancer (cancer and leukemia group B 30602). J Thorac Oncol. 2010;5(3):380–4.

    Article  PubMed  Google Scholar 

  58. Roelle S, Grosse R, Buech T, Chubanov V, Gudermann T. Essential role of Pyk2 and Src kinase activation in neuropeptide-induced proliferation of small cell lung cancer cells. Oncogene. 2008;27(12):1737–48.

    Article  PubMed  CAS  Google Scholar 

  59. Rosen N, Bolen JB, Schwartz AM, Cohen P, DeSeau V, Israel MA. Analysis of pp 60c-src protein kinase activity in human tumor cell lines and tissues. J Biol Chem. 1986;261(29):13754–9.

    PubMed  CAS  Google Scholar 

  60. Jiang SX, Sato Y, Kuwao S, Kameya T. Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas. J Pathol. 1995;177(2):135–8.

    Article  PubMed  CAS  Google Scholar 

  61. Hurwitz JL, McCoy F, Scullin P, Fennell DA. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009;14(10):986–94.

    Article  PubMed  CAS  Google Scholar 

  62. Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1997;139(5):1281–92.

    Article  PubMed  CAS  Google Scholar 

  63. Huang DC, Strasser A. BH3-Only proteins-essential initiators of apoptotic cell death. Cell. 2000;103(6):839–42.

    Article  PubMed  CAS  Google Scholar 

  64. Rudin CM, Salgia R, Wang X, Hodgson LD, Masters GA, Green M, et al. 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. 2008;26(6):870–6.

    Article  PubMed  CAS  Google Scholar 

  65. Langer CJ, Albert PKI, Blakely LJ, Pajkos G, Petrov P, Somfay A, et al. A randomized phase II study of carboplatin (C) and etoposide (E) with or without pan-BCL-2 antagonist obatoclax (Ob) in extensive-stage small cell lung cancer (ES-SCLC). J Clin Oncol. 2011; 29(suppl; abstr 7001). 2011 ASCO Annual Meeting.

    Google Scholar 

  66. Bruzzese F, Rocco M, Castelli S, Di Gennaro E, Desideri A, Budillon A. Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis. Mol Cancer Ther. 2009;8(11):3075–87.

    Article  PubMed  CAS  Google Scholar 

  67. Gray J, Cubitt CL, Zhang S, Chiappori A. Combination of HDAC and topoisomerase inhibitors in small cell lung cancer. Cancer Biol Ther. 2012;13(8):614–22.

    Article  PubMed  CAS  Google Scholar 

  68. NCT00702962-Carboplatin and etoposide in combination with vorinostat for patients with extensive stage small cell lung cancer. www.clinicaltrials.gov.

  69. NCT00926640-A phase I study of belinostat in combination with cisplatin and etoposide in adults with small cell lung carcinoma and other advanced cancers. www.clinicaltrials.gov.

  70. Watkins DN, Berman DM, Baylin SB. Hedgehog signaling: progenitor phenotype in small-cell lung cancer. Cell Cycle. 2003;2(3):196–8.

    Article  PubMed  CAS  Google Scholar 

  71. Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, et al. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med. 2011;17(11):1504–8.

    Article  PubMed  CAS  Google Scholar 

  72. NCT00887159-Cisplatin and etoposide phosphate with or without gdc-0449 or cixutumumab in treating patients with extensive-stage small cell lung cancer. www.clinicaltrials.gov.

  73. Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, Corbeil J, et al. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res. 2008;14(1):309–17.

    Article  PubMed  CAS  Google Scholar 

  74. Koster W, Heider A, Niederle N, Wilke H, Stamatis G, Fischer JR, et al. Phase II trial with carboplatin and bendamustine in patients with extensive stage small-cell lung cancer. J Thorac Oncol. 2007;2(4):312–6.

    Article  PubMed  Google Scholar 

  75. Venepalli NK, Hutchison AS, Carbone DP, Johnson DH, Keedy VL, Pao W, et al. A phase II study of second-line bendamustine in relapsed or refractory small cell lung cancer (SCLC). J Clin Oncol. 2011; 29: (suppl; abstr e17505) [serial on the Internet].

    Google Scholar 

  76. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(19):3213–21.

    Article  PubMed  Google Scholar 

  77. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91.

    Article  PubMed  CAS  Google Scholar 

  78. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14(19):6302–9.

    Article  PubMed  Google Scholar 

  79. Krebs MG, Sloane R, Priest L, Lancashire L, Hou JM, Greystoke A, et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J Clin Oncol. 2011;29(12):1556–63.

    Article  PubMed  Google Scholar 

  80. Kularatne BY, Lorigan P, Browne S, Suvarna SK, Smith MO, Lawry J. Monitoring tumour cells in the peripheral blood of small cell lung cancer patients. Cytometry. 2002;50(3):160–7.

    Article  PubMed  CAS  Google Scholar 

  81. Hou JM, Greystoke A, Lancashire L, Cummings J, Ward T, Board R, et al. Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. Am J Pathol. 2009;175(2):808–16.

    Article  PubMed  CAS  Google Scholar 

  82. Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol. 2012;30(5):525–32.

    Article  PubMed  Google Scholar 

  83. Naito T, Tanaka F, Ono A, Yoneda K, Takahashi T, Murakami H, et al. Prognostic impact of ­circulating tumor cells in patients with small cell lung cancer. J Thorac Oncol. 2012;7(3):512–9.

    Article  PubMed  Google Scholar 

  84. Bogos K, Renyi-Vamos F, Dobos J, Kenessey I, Tovari J, Timar J, et al. High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer. Clin Cancer Res. 2009;15(5):1741–6.

    Article  PubMed  CAS  Google Scholar 

  85. Yang X, Wang D, Yang Z, Qing Y, Zhang Z, Wang G, et al. CEA is an independent prognostic indicator that is associated with reduced survival and liver metastases in SCLC. Cell Biochem Biophys. 2011;59(2):113–9.

    Article  PubMed  CAS  Google Scholar 

  86. Pujol JL, Quantin X, Jacot W, Boher JM, Grenier J, Lamy PJ. Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer. Lung Cancer. 2003;39(2):131–8.

    Article  PubMed  Google Scholar 

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  1. Department of Medicine, Penn State Hershey Medical Center, 500 University Drive, CH72, Hershey, PA, 17033, USA

    Monika Joshi M.D., Ayodele Ayoola M.D. & Chandra P. Belani M.D.

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    Wafik S El-Deiry

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Joshi, M., Ayoola, A., Belani, C.P. (2013). Small-Cell Lung Cancer: An Update on Targeted Therapies. In: El-Deiry, W. (eds) Impact of Genetic Targets on Cancer Therapy. Advances in Experimental Medicine and Biology, vol 779. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6176-0_18

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