Review: Targeted therapies in small cell lung cancer: A review

Therapeutic Advances in Medical Oncology

Volumn 2, Issue 1, 2010, Pages 25-37

  Abidin, Aidalena Z ^a   Califano, Raffaele ^a   Harle, Amelie ^a   Garassino, Marina C ^b   Blackhall, Fiona ^a  

^a CHRISTIE HOSPITAL   (United Kingdom)

^b FATEBENEFRATELLI HOSPITAL   (Italy)

Author keywords

angiogenesis inhibitors; apoptosis promoters; BH3 mimetics; cell signalling inhibitors; MET inhibitors; multidrug resistance inhibitors; small cell lung cancer (SCLC); targeted therapies; vaccines

Indexed keywords

4 (8 CYCLOPENTYL 7 ETHYL 5,6,7,8 TETRAHYDRO 5 METHYL 6 OXO 2 PTERIDINYLAMINO) 3 METHOXY N (1 METHYL 4 PIPERIDINYL)BENZAMIDE; 4 [4 [2 (4 CHLOROPHENYL) 5,5 DIMETHYL 1 CYCLOHEXEN 1 YLMETHYL] 1 PIPERAZINYL] N [4 [3 MORPHOLINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 (TRIFLUOROMETHYLSULFONYL)BENZENESULFONYL]BENZAMIDE; AFINITOR; AFLIBERCEPT; AMG 102; AMG 479; ANTINEOPLASTIC AGENT; BB 10901; BELINOSTAT; BEVACIZUMAB; BIRICODAR; BORTEZOMIB; CEDIRANIB; CP 751871; DASATINIB; EVEROLIMUS; GDC 0449; GEFITINIB; IMATINIB; IMC A12; ISOSORBIDE; MARIMASTAT; N (5 CHLORO 1,3 BENZODIOXOL 4 YL) 7 [2 (4 METHYL 1 PIPERAZINYL)ETHOXY] 5 (TETRAHYDRO 2H PYRAN 4 YLOXY) 4 QUINAZOLINAMINE; OBATOCLAX; OBLIMERSEN; SNDX 275; SORAFENIB; SUNITINIB; TANOMASTAT; TEMSIROLIMUS; THALIDOMIDE; TIPIFARNIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VORINOSTAT;

AERODIGESTIVE FISTULA; APOPTOSIS; BLOOD TOXICITY; CANCER RADIOTHERAPY; CANCER THERAPY; CHRONIC MYELOID LEUKEMIA; CLINICAL ASSESSMENT; CLINICAL TRIAL; DIGESTIVE SYSTEM FISTULA; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; ESOPHAGITIS; FLU LIKE SYNDROME; GASTROINTESTINAL STROMAL TUMOR; HUMAN; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; NEUROPATHY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; SKIN TOXICITY; THROMBOSIS; TRACHEOESOPHAGEAL FISTULA; UNSPECIFIED SIDE EFFECT;

EID: 77953406115     PISSN: 17588340     EISSN: None     Source Type: Journal    
DOI: 10.1177/1758834009356014     Document Type: Review

References (86)

1. Antonia, S.J., Mirza, N., Fricke, I., Chiappori, A., Thompson, P., Williams, N. et al. (2006) Combination of P 53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12: 878-887.
2. Arnold, A.M., Seymour, L., Smylie, M., Ding, K., Ung, Y., Findlay, B. 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: 4278-4284.
3. Besse, B., Suk Heist, R., Papadimitrakopoulou, V., Camidge, D., Beck, J.T., Schmid, P. et al. (2009) Phase I dose-escalation study investigating Rad 001 (R) in combination with cisplatin (C) and etoposide (E) in previously untreated patients with extensive-stage disease small-cell lung cancer (ED-SCLC), 13th World Conference on Lung Cancer. San Francisco, California, USA.
4. Blackhall, F.H. and Shepherd, F.A. ( 2004) Angiogenesis inhibitors in the treatment of small cell and non-small cell lung cancer. Hematol Oncol Clin North Am 18: 1121-1141, ix.
5. Blackhall, F.H., Pintilie, M., Michael, M., Leighl, N., Feld, R., Tsao, M.S. 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: 2241-2247.
6. Demetri, G.D., Von Mehren, M., Blanke, C.D., van Den Abbeele, A.D., Eisenberg, B., Roberts, P.J. et al. (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472-480.
7. Druker, B.J., Guilhot, F., O’Brien, S.G., Gathmann, I., Kantarjian, H., Gattermann, N. et al. (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355: 2408-2417.
8. Fossella, F., Woll, P., Lorigan, P., Tolcher, A., O’Brien, M., O’Keeffe, J. et al. (2009) Clinical Experience of Imgn 901 (Bb-10901) in patients with small cell lung carcinoma (SCLC), 13th World Conference on Lung Cancer. San Francisco, California, USA.
9. Gandhi, L., Chu, Q.S., Stephenson, J., Johnson, B.E., Govindan, R., Bonomi, P. et al. (2009) An open label phase II trial of the Plk 1 inhibitor Bi 2536, in patients with sensitive relapse small cell lung cancer (SCLC). J Clin Oncol (Meeting Abstracts) 27: 8108.
10. Giaccone, G., Debruyne, C., Felip, E., Chapman, P.B., Grant, S.C., Millward, M. et al. (2005) Phase III study of adjuvant vaccination with Bec 2/Bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971b; Silva Study). J Clin Oncol 23: 6854-6864.
11. Gitlitz, B.J., Glisson, B.S., Moon, J., Reimers, H. and Gandara, D.R. ( 2008) Sorafenib in patients with platinum (plat) treated extensive stage small cell lung cancer (E-SCLC): A Swog (S0435) phase II trial. J Clin Oncol (Meeting Abstracts) 26: 8039.
12. Greystoke, A., Cummings, J., Ward, T., Simpson, K., Renehan, A., Butt, F. et al. (2008) Optimisation of circulating biomarkers of cell death for routine clinical use. Ann Oncol 19: 990-995.
13. Griffiths, R., Lorigan, P., Thatcher, N. and Blackhall, F. ( 2008) Update on targeted therapies for small cell carcinoma of the lung. Target Oncol 3: 205-215.
14. Hann, C.L., Daniel, V.C., Sugar, E.A., Dobromilskaya, I., Murphy, S.C., Cope, L. et al. (2008) Therapeutic efficacy of Abt-737, a selective inhibitor of Bcl-2, in small cell lung cancer. Cancer Res 68: 2321-2328.
15. Heist, R.S., Fain, J., Chinnasami, B., Khan, W., Molina, J., Brainerd, V. et al. (2009) A phase I/II (P1/P2) study of at-101 in combination with topotecan (t) in patients with relapsed or refractory small cell lung cancer (SCLC) after prior platinum-containing first-line chemotherapy. J Clin Oncol (Meeting Abstracts) 27: 8106.
16. Heymach, J.V., Johnson, D.H., Khuri, F.R., Safran, H., Schlabach, L.L., Yunus, F. et al. (2004) Phase II study of the farnesyl transferase inhibitor R 115777 in patients with sensitive relapse small-cell lung cancer. Ann Oncol 15: 1187-1193.
17. Hou, J.M., Greystoke, A., Lancashire, L., Cummings, J., Ward, T., Board, R. et al. (2009) Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. Am J Pathol 175: 808-816.
18. Jackman, D.M. and Johnson, B.E. ( 2005) Small-cell lung cancer. Lancet 366: 1385-1396.
19. Jiang, S.X., Kameya, T., Sato, Y., Yanase, N., Yoshimura, H. and Kodama, T. ( 1996) Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. Am J Pathol 148: 837-846.
20. Johnson, B.E., Fischer, T., Fischer, B., Dunlop, D., Rischin, D., Silberman, S. et al. (2003) Phase II study of imatinib in patients with small cell lung cancer. Clin Cancer Res 9: 5880-5887.
21. Johnson, F.M., Krug, L.M., Tran, H.T., Shoaf, S., Prieto, V.G., Tamboli, P. et al. (2006) Phase I studies of imatinib mesylate combined with cisplatin and irinotecan in patients with small cell lung carcinoma. Cancer 106: 366-374.
22. Kotsakis, A., Tarhini, A., Petro, D., Flaugh, R., Vallabhaneni, G., Belani, C. et al. (2009) Phase II study of Rad 001 (Everolimus) in previously treated small cell lung cancer (SCLC), 13th World Conference on Lung Cancer. San Francisco, California, USA.
23. Krug, L.M., Crapanzano, J.P., Azzoli, C.G., Miller, V.A., Rizvi, N., Gomez, J. et al. (2005) Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer 103: 2128-2131.
24. Krystal, G.W., Honsawek, S., Litz, J. and Buchdunger, E. ( 2000) The selective tyrosine kinase inhibitor sti 571 inhibits small cell lung cancer growth. Clin Cancer Res 6: 3319-3326.
25. Kusmartsev, S., Cheng, F., Yu, B., Nefedova, Y., Sotomayor, E., Lush, R. et al. (2003) All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 63: 4441-4449.
26. Lee, S.-M., Woll, P.J., James, L.E., Hatton, M., Ali, K., Spiro, S.G. et al. (2007) A phase III randomised, double blind, placebo controlled trial of etoposide/carboplatin with or without thalidomide in advanced small cell lung cancer (SCLC): Prs-04. JThorac Oncol 2: S306-S307, DOI: 310.1097/1001.JTO.0000283089. 0000256099.0000283079.
27. Lynch Jr, T.J., Lambert, J.M., Coral, F., Shefner, J., Wen, P., Blattler, W.A. et al. (1997) Immunotoxin therapy of small-cell lung cancer: a phase I study of n 901-blocked ricin. J Clin Oncol 15: 723-734.
28. Ma, P.C., Kijima, T., Maulik, G., Fox, E.A., Sattler, M., Griffin, J.D. et al. (2003) C-Met mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63: 6272-6281.
29. Macaulay, V.M., Everard, M.J., Teale, J.D., Trott, P.A., van Wyk, J.J., Smith, I.E. 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: 2511-2517.
30. Maulik, G., Kijima, T., Ma, P.C., Ghosh, S.K., Lin, J., Shapiro, G.I. et al. (2002) Modulation of the C-Met/ hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res 8: 620-627.
31. Mok, T.S., Wu, Y.L., Thongprasert, S., Yang, C.H., Chu, D.T., Saijo, N. et al. (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361: 947-957.
32. Molina, J., Foster, N., Nelson, G., Grain Ger, A., Steen, P., Nikcevich, D. et al. (2009) Phase II trial (N0621) of the C-Src Inhibitor azd-0530 after 4 cycles of chemotherapy for patients with extensive stage small cell lung cancer (ED-SCLC), 13th World Conference on Lung Cancer. San Francisco, California, USA.
33. Moore, A.M., Einhorn, L.H., Estes, D., Govindan, R., Axelson, J., Vinson, J. 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: 93-97.
34. Mortenson, M.M., Schlieman, M.G., Virudachalam, S., Lara, P.N., Gandara, D.G., Davies, A.M. et al. (2005) Reduction in Bcl-2 Levels by 26s proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer. Lung Cancer 49: 163-170.
35. NCT00068484. Topotecan and bortezomib in treating patients with metastatic or unresectable cancer. www.clinicaltrials.gov
36. NCT00182689. Sorafenib in treating patients with extensive stage small cell lung cancer.www.clinicaltrials.gov
37. NCT00308529. Irinotecan, carboplatin, bevacizumab and radiation therapy in the treatment of limited stage small cell lung cancer. www.clinicaltrials.gov
38. NCT00317200. A study of paclitaxel plus bevacizumab in patients with chemosensitive relapsed small cell lung cancer. www.clinicaltrials.gov
39. NCT00388089. Bortezomib and topotecan in treating patients with advanced solid tumors. www.clinicaltrials.gov
40. NCT00453154. Sunitinib, cisplatin or carboplatin, and etoposide in treating patients with extensive-stage small cell lung cancer. www.clinicaltrials.gov
41. NCT00466232. Phase I study of weekly topotecan in combination with sorafenib in treatment of relapsed small cell lung cancer. www.clinicaltrials.gov
42. NCT00521144. Obatoclax mesylate and topotecan in treating patients with relapsed or refractory small cell lung cancer or advanced solid tumours. www.clinicaltrials.gov
43. NCT00528645. Azd0530 in treating patients with extensive stage small cell lung cancer. www.clinicaltrials.gov
44. NCT00541359. Bortezomib and topotecan in treating patients with advanced solid tumors. www.clinicaltrials.gov
45. NCT00613626. Cisplatin and etoposide +/concurrent vandetanib in previously untreated extensive stage small cell lung cancer. www.clinicaltrials.gov
46. NCT00616109. Sunitinib maintenance therapy after induction platinum-based chemotherapy in patients with extensive-stage small cell lung cancer. www.clinicaltrials.gov
47. NCT00618891. Vaccine therapy and chemotherapy with or without tretinoin in treating patients with extensive-stage small cell lung cancer. www.clinicaltrials.gov
48. NCT00620347. Sunitinib as a second-line treatment for patients with extensive-disease small cell lung cancer (ED-SCLC). www.clinicaltrials.gov
49. NCT00682981. A phase I/II study of carboplatin and etoposide with or without obatoclax in extensive stage small cell lung cancer (ES-SCLC). www.clinicaltrials.gov
50. NCT00697476. Study of oral vorinostat in combination with topotecan in patients with chemosensitive recurrent small cell lung cancer (SCLC). www.clinicaltrials.gov
51. NCT00702962. Carboplatin and etoposide in combination with vorinostat for patients with extensive stage small cell lung cancer. www.clinicaltrials.gov
52. NCT00761696. A phase 1 study of ipi-926 in patients with advanced and/or metastatic solid tumor malignancies. www.clinicaltrials.gov
53. NCT00770731. Study of temsirolimus, topotecan, and bortezomib. www.clinicaltrials.gov
54. 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
55. NCT00828139. Topotecan with or without aflibercept in treating patients with extensive-stage small cell lung cancer. www.clinicaltrials.gov
56. 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
57. 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
58. Owonikoko, T.K., Stoller, R.G., Petro, D., Flaugh, R., Hershberger, P.A., Belani, C.P. et al. (2008) Phase II study of Rad 001 (everolimus) in previously treated small cell lung cancer (SCLC). J Clin Oncol (Meeting Abstracts) 26: 19017.
59. Pandya, K.J., Dahlberg, S., Hidalgo, M., Cohen, R.B., Lee, M.W., Schiller, J.H. et al. (2007) 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 2: 1036-1041.
60. Patton, J.F., Spigel, D.R., Greco, F.A., Liggett, W.H., Zubkus, J.D., Baskette, M. et al. (2006) 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 (Meeting Abstracts) 24: 7085.
61. Peck, R.A., Hewett, J., Harding, M.W., Wang, Y.M., Chaturvedi, P.R., Bhatnagar, A. et al. (2001) Phase I and pharmacokinetic study of the novel mdr 1 and mrp 1 inhibitor biricodar administered alone and in combination with doxorubicin. J Clin Oncol 19: 3130-3141.
62. Potti, A., Moazzam, N., Ramar, K., Hanekom, D.S., Kargas, S. and Koch, M. ( 2003) Cd117 (C-Kit) overexpression in patients with extensive-stage small-cell lung carcinoma. Ann Oncol 14: 894-897.
63. Pujol, J.L., Breton, J.L., Gervais, R., Tanguy, M.L., Quoix, E., David, P. 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 Cleo 04 Ifct 00-01. J Clin Oncol 25: 3945-3951.
64. Ramalingam, S.S., Mack, P.C., Vokes, E.E., Longmate, J., Govindan, R., Koczywas, M. et al. (2008) Cediranib (Azd2171) for the treatment of recurrent small cell lung cancer (SCLC): a California Consortium phase II study (Nci # 7097). J Clin Oncol (Meeting Abstracts) 26: 8078.
65. Ready, N., Dudek, A.Z., Wang, X.F., Graziano, S., Green, M.R. and Vokes, E.E. ( 2007) Calgb 30306: a phase II study of cisplatin (C), irinotecan (I) and bevacizumab (B) for untreated extensive stage small cell lung cancer (ES-SCLC). J Clin Oncol (Meeting Abstracts) 25: 7563.
66. Rigas, J.R., Denham, C.A., Rinaldi, D., Moore, T., Smith Ii, J.W., Winston, R.D. et al. (2003) O-107 adjuvant targeted therapy in unresectable lung cancer: the results of two randomized placebo-controlled trials of bay 12-9566, a matrix metalloproteinase inhibitor (MMPI). Lung Cancer 41: S34-S34.
67. Rossi, A., Maione, P., Colantuoni, G., Ferrara, C., Rossi, E., Guerriero, C. et al. (2009) Recent developments of targeted therapies in the treatment of non-small cell lung cancer. Curr Drug Discov Technol 6: 91-102.
68. Rudin, C.M., Salgia, R., Wang, X., Hodgson, L.D., Masters, G.A., Green, M. 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: 870-876.
69. Salven, P., Ruotsalainen, T., Mattson, K. and 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: 144-146.
70. Sandler, A., Szwaric, S., Dowlati, A., Moore Jr, D.F. and Schiller, J.H. ( 2007) 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) 25: 7564.
71. Schneider, B.J., Gadgeel, S., Ramnath, N., Worden, F.P., Wozniak, A., Ruckdeschel, J. et al. (2006) Phase II trial of imatinib maintenance therapy after irinotecan and cisplatin in patients with c-kit positive extensive-stage small cell lung cancer (ES SCLC). J Clin Oncol (Meeting Abstracts) 24: 17089.
72. Schrump, D.S., Fischette, M.R., Nguyen, D.M., Zhao, M., Li, X., Kunst, T.F. et al. (2008) Clinical and molecular responses in lung cancer patients receiving romidepsin. Clin Cancer Res 14: 188-198.
73. Shepherd, F.A., Giaccone, G., Seymour, L., Debruyne, C., Bezjak, A., Hirsh, V. et al. (2002) Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol 20: 4434-4439.
74. Shepherd, F.A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E.H., Hirsh, V., Thongprasert, S. et al. (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353: 123-132.
75. Sher, T., Dy, G.K. and Adjei, A.A. ( 2008) Small cell lung cancer. Mayo Clin Proc 83: 355-367.
76. Slotman, B., Faivre-Finn, C., Kramer, G., Rankin, E., Snee, M., Hatton, M. et al. (2007) Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357: 664-672.
77. Spigel, D.R., Hainsworth, J.D., Farley, C., Meng, C., Blake, D., Burris, III H.A. et al. (2008) Tracheoesophageal (Te) fistula development in a phase II trial of concurrent chemoradiation (crt) and bevacizumab (b) in limited-stage small-cell lung cancer (LS-SCLC). J Clin Oncol (Meeting Abstracts) 26: 7554.
78. Spigel, D., Townley, P., Waterhouse, D., Fang, L., Adiguzel, I., Huang, J. et al. (2009) Salute: a placebo-controlled, double-blind, multicenter, randomized, phase II study of bevacizumab in previously untreated extensive-stage small cell lung cancer (SCLC), 13th World Conference on Lung Cancer. San Francisco, California, USA.
79. Takigawa, N., Segawa, Y., Maeda, Y., Takata, I. and Fujimoto, N. ( 1997) Serum hepatocyte growth factor/scatter factor levels in small cell lung cancer patients. Lung Cancer 17: 211-218.
80. Turrisi 3rd, A.T., Kim, K., Blum, R., Sause, W.T., Livingston, R.B., Komaki, R. et al. (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340: 265-271.
81. Von Hoff, D.D., Lorusso, P.M., Rudin, C.M., Reddy, J.C., Yauch, R.L., Tibes, R. et al. (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361: 1164-1172.
82. Warshamana-Greene, G.S., Litz, J., Buchdunger, E., Hofmann, F., Garcia-Echeverria, C. and Krystal, G.W. ( 2004) The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor nvp-adw742, in combination with sti 571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling. Mol Cancer Ther 3: 527-535.
83. Watkins, D.N., Berman, D.M., Burkholder, S.G., Wang, B., Beachy, P.A. and Baylin, S.B. ( 2003) Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 422: 313-317.
84. Yan, J.J., Chen, F.F., Tsai, Y.C. and Jin, Y.T. ( 1996) Immunohistochemical detection of bcl-2 protein in small cell carcinomas. Oncology 53: 6-11.
85. Zangemeister-Wittke, U., Schenker, T., Luedke, G.H. and Stahel, R.A. ( 1998) Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines. Br J Cancer 78: 1035-1042.
86. Zelen, M. ( 1973) Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 3 4: 31-42.