Non-small-cell lung cancer: Molecular targeted therapy and personalized medicine - Drug resistance, mechanisms, and strategies

Pharmacogenomics and Personalized Medicine

Volumn 6, Issue 1, 2013, Pages 25-36

  Sechler, Marybeth ^a   Cizmic, Amber D ^b   Avasarala, Sreedevi ^a   Van Scoyk, Michelle ^a   Brzezinski, Christine ^a   Kelley, Nicole ^a   Bikkavilli, Rama Kamesh ^a   Winn, Robert A ^a,b  

^a UNIVERSITY OF COLORADO   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Drug targets; Lung cancer; NSCLC; Personalized medicine

Indexed keywords

5 (2,4 DIHYDROXY 5 ISOPROPYLPHENYL) 4 (4 MORPHOLINOMETHYLPHENYL) 3 ISOXAZOLECARBOXYLIC ACID ETHYLAMIDE; ANAPLASTIC LYMPHOMA KINASE; ANGIOGENESIS INHIBITOR; ARRY 142866; BEVACIZUMAB; CARBOPLATIN; CELECOXIB; CETUXIMAB; CISPLATIN; CIXUTUMUMAB; CRIZOTINIB; DASATINIB; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; ETOPOSIDE; GEFITINIB; HISTONE DEACETYLASE INHIBITOR; LINIFANIB; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; NAVELBINE; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PLACEBO; PROTEIN FARNESYLTRANSFERASE INHIBITOR; SELUMETINIB; SORAFENIB; SUNITINIB; TIVANTINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

AMINO ACID SUBSTITUTION; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RESISTANCE; COLORECTAL CANCER; DRUG EFFICACY; DRUG SAFETY; GENE MUTATION; HETEROZYGOTE; HUMAN; HYPOGONADISM; LIVER TOXICITY; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; LUNG SQUAMOUS CELL CARCINOMA; MOLECULARLY TARGETED THERAPY; NONHUMAN; ONCOGENE K RAS; OVERALL SURVIVAL; PERSONALIZED MEDICINE; PROGRESSION FREE SURVIVAL; REVIEW; SURVIVAL TIME; UNSPECIFIED SIDE EFFECT;

EID: 84875974511     PISSN: None     EISSN: 11787066     Source Type: Journal    
DOI: 10.2147/PGPM.S26058     Document Type: Review

References (131)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10-29.
2. Okubo K, Mark EJ, Flieder D, etal. Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival. J Thorac Cardiovasc Surg. 1999;118:702-709.
3. Raz DJ, He B, Rosell R, Jablons DM. Current concepts in bronchioloalveolar carcinoma biology. Clin Cancer Res. 2006;12:3698-3704.
4. Siegel R, DeSantis C, Virgo K, etal. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62:220-241.
5. Khuri FR, Herbst RS, Fossella FV. Emerging therapies in non-small-cell lung cancer. Ann Oncol. 2001;12:739-744.
6. Weinstein IB. Cancer. Addiction to oncogenes-the Achilles heal of cancer. Science. 2002;297:63-64.
7. Habeck M. FDA licences imatinib mesylate for CML. Lancet Oncol. 2002;3:6.
8. Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem. 1990;265: 7709-7712.
9. Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003;8:303-306.
10. Cohen MH, Johnson JR, Chen YF, Sridhara R, Pazdur R. FDA drug approval summary: erlotinib (Tarceva) tablets. Oncologist. 2005;10: 461-466.
11. Thatcher N, Chang A, Parikh P, etal. 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.
12. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, etal. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353: 123-132.
13. Gazdar AF. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009;28 Suppl 1:S24-S31.
14. Lynch TJ, Bell DW, Sordella R, etal. 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.
15. Marchetti A, Martella C, Felicioni L, etal. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol. 2005;23:857-865.
16. Paez JG, Jänne PA, Lee JC, etal. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497-1500.
17. Wu YL, Zhong WZ, Li LY, etal. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol. 2007;2:430-439.
18. Shao YY, Lin CC, Yang CH. Gefitinib or erlotinib in the treatment of advanced non-small cell lung cancer. Discov Med. 2010;9: 538-545.
19. Costa EC, Taron M, Queralt C, etal. Differential progression-free survival (PFS) to erlotinib according to EGFR exon 19 deletion type in non-small cell lung cancer (NSCLC) patients (p) in the EURTAC study. J Clin Oncol. 2012;30 Suppl:7540.
20. Mok TS, Wu YL, Thongprasert S, etal. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-957.
21. Oxnard GR, Arcila ME, Sima CS, etal. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011;17:1616-1622.
22. Rosell R, Moran T, Queralt C, etal. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med. 2009;361: 958-967.
23. Yun CH, Mengwasser KE, Toms AV, etal. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A. 2008;105:2070-2075.
24. Pao W, Miller VA, Politi KA, etal. 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.
25. Kosaka T, Yatabe Y, Endoh H, etal. Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res. 2006;12: 5764-5769.
26. Hammerman PS, Janne PA, Johnson BE. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res. 2009;15:7502-7509.
27. Suda K, Mizuuchi H, Maehara Y, Mitsudomi T. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation-diversity, ductility, and destiny. Cancer Metastasis Rev. 2012;31:807-814.
28. Engelman JA, Zejnullahu K, Mitsudomi T, etal. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039-1043.
29. Cappuzzo F, Jänne PA, Skokan M, etal. MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients. Ann Oncol. 2009;20:298-304.
30. Kosaka T, Yamaki E, Mogi A, Kuwano H. Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in non-small-cell lung cancer. J Biomed Biotechnol. 2011;2011:165214.
31. Sos ML, Koker M, Weir BA, etal. PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res. 2009;69:3256-3261.
32. Thomson S, Buck E, Petti F, etal. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res. 2005;65:9455-9462.
33. Chang TH, Tsai MF, Su KY, etal. Slug confers resistance to the epidermal growth factor receptor tyrosine kinase inhibitor. Am J Respir Crit Care Med. 2011;183:1071-1079.
34. Winn RA, Tuder RM. "Un-slugging" resistance to epidermal growth factor receptor inhibition. A positive outlook for the future of lung cancer therapy. Am J Respir Crit Care Med. 2011;183:970-972.
35. Ng KP, Hillmer AM, Chuah CT, etal. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med. 2012;18:521-528.
36. Pao W, Wang TY, Riely GJ, etal. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2:e17.
37. Massarelli E, Varella-Garcia M, Tang X, etal. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res. 2007;13:2890-2896.
38. Schmid K, Oehl N, Wrba F, Pirker R, Pirker C, Filipits M. EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res. 2009;15:4554-4560.
39. Shigematsu H, Lin L, Takahashi T, etal. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005;97:339-346.
40. Kris MG, Johnson BE, Kwiatkowski, etal. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: the NCI's Lung Cancer Mutation Consortium (LCMC). J Clin Oncol. 2011;29 Suppl:CRA7506.
41. Broker LE, Giaccone G. The role of new agents in the treatment of non-small cell lung cancer. Eur J Cancer. 2002;38:2347-2361.
42. Engelman JA, Chen L, Tan X, etal. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med. 2008;14:1351-1356.
43. Jänne PA, Shaw AT, Pereira JR, etal. Efficacy and patient (pt)-reported outcomes (PROs) with selumetinib (AZD6244, ARRY-142866; SEL) + docetaxel (Doc) in KRAS-mutant advanced non-small cell lung cancer (NSCLC): a randomized, phase II trial. Ann Oncol. 2012;23 Suppl 9: 1233PD.
44. Ramalingam S, Belani CP. Recent advances in targeted therapy for non-small cell lung cancer. Expert Opin Ther Targets. 2007;11:245-257.
45. Rosell R, Robinet G, Szczesna A, etal. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol. 2008;19:362-369.
46. Pirker R, Pereira JR, Szczesna A, etal. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373:1525-1531.
47. Hanna NH, Dahlberg SE, Kolesar J, etal. Three-arm randomized phase II study of carboplatin (C) and paclitaxel (P) in combination with cetuximab (CET), IMC-A12, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: an Eastern Cooperative Oncology Group (ECOG) study (E4508). J Clin Oncol. 2012;30 Suppl:7516.
48. Greillier L, Martel-Lafay I, Arpin D, etal. A randomised phase II study of cetuximab (c) in combination with two cisplatin-based concurrent chemoradiotherapy regimens in patients (pts) with stage III non-small cell lung cancer (NSCLC). Final results of the GFPC 08-03 trial. Paper presented at the 37th European Society for Medical Oncology (ESMO) Congress; September 28-October 2, 2012; Vienna, Austria.
49. Gridelli C, Maione P, Ferrara ML, Rossi A. Cetuximab and other anti-epidermal growth factor receptor monoclonal antibodies in the treatment of non-small cell lung cancer. Oncologist. 2009;14:601-611.
50. Ma PC. Personalized targeted therapy in advanced non-small cell lung cancer. Cleve Clin J Med. 2012;79 Suppl 1:eS56-eS60.
51. Soda M, Choi YL, Enomoto M, etal. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561-566.
52. Koivunen JP, Mermel C, Zejnullahu K, etal. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008;14:4275-4283.
53. Kwak EL, Bang YJ, Camidge DR, etal. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363: 1693-1703.
54. Forde PM, Rudin CM. Crizotinib in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother. 2012;13:1195-1201.
55. Galetta D, Rossi A, Pisconti S, Colucci G. The emerging role of ALK inhibitors in the treatment of advanced non-small cell lung cancer. Expert Opin Ther Targets. 2012;16 Suppl 2:S45-S54.
56. Kimura H, etal. ALK fusion gene positive lung cancer and 3 cases treated with an inhibitor for ALK kinase activity. Lung Cancer. 2012;75: 66-72.
57. Takeuchi K, Choi YL, Togashi Y, etal. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res. 2009;15:3143-3149.
58. Togashi Y, Soda M, Sakata S, etal. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One. 2012;7:e31323.
59. Weickhardt AJ, Rothman MS, Salian-Mehta S, etal. Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012;118:5302-5309.
60. Schnell P, Safferman AZ, Bartlett CH, Tang Y, Wilner KD. Clinical presentation of hepatotoxicity-associated crizotinib in ALK-positive (ALK+) advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2012;30 Suppl:7598.
61. Zhang S, Wang F, Keats J, etal. Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chem Biol Drug Des. 2011;78:999-1005.
62. Doebele RC, Pilling AB, Aisner DL, etal. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18:1472-1482.
63. Katayama R, Shaw AT, Khan TM, etal. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4:120ra17.
64. Camidge DR, Doebele RC. Treating ALK-positive lung cancer-early successes and future challenges. Nat Rev Clin Oncol. 2012;9: 268-277.
65. Chen Z, Sasaki T, Tan X, etal. Inhibition of ALK, PI3K/MEK, and HSP90in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 2010;70:9827-9836.
66. Katayama R, Khan TM, Benes C, etal. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011;108: 7535-7540.
67. Garon EB, Moran T, Barlesi F, etal. Phase II study of the HSP90inhibitor AUY922in patients with previously treated, advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2012;30 Suppl:7543.
68. Sasaki T, Janne PA. New strategies for treatment of ALK-rearranged non-small cell lung cancers. Clin Cancer Res. 2011;17:7213-7218.
69. Heuckmann JM, Hölzel M, Sos ML, etal. ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res. 2011;17:7394-7401.
70. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100: 57-70.
71. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4-6.
72. Reck M, Gatzemeier U. Targeted therapies: thalidomide in lung cancer therapy-what have we learned? Nat Rev Clin Oncol. 2010;7: 134-135.
73. Hoang T, Dahlberg SE, Schiller JH, etal. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012;30:616-622.
74. Yang JC, Haworth L, Sherry RM, etal. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427-434.
75. Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr Treat Options Oncol. 2001;2:459-471.
76. Azim HA Jr, Ganti AK. Targeted therapy in advanced non-small cell lung cancer (NSCLC): where do we stand? Cancer Treat Rev. 2006;32:630-636.
77. Laskin JJ, Sandler AB. First-line treatment for advanced non-small-cell lung cancer. Oncology (Williston Park). 2005;19:1671-1676; discussion 1678-1680.
78. Dempke WC, Suto T, Reck M. Targeted therapies for non-small cell lung cancer. Lung Cancer. 2010;67:257-274.
79. Stevenson JP, Langer CJ, Somer RA, etal. Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer. Cancer. 2012;118:5580-5587.
80. Roehr B. Bevacizumab as adjuvant therapy for lung cancer does not help patients over 65. BMJ. 2012;344:e2855.
81. Dasanu CA. Bevacizumab in lung cancer: lackluster performance and unjustified expense? J Oncol Pharm Pract. 2012;18:381-382.
82. Ohyanagi F, Tanimoto A, Sakatani T, etal. Phase II trial of bevacizumab plus docetaxel in patients with previously treated nonsquamous non-small cell lung cancer. J Clin Oncol. 2012;30 Suppl:e18004.
83. Ramalingam SS, Owonikoko TK, Khuri FR. Lung cancer: new biological insights and recent therapeutic advances. CA Cancer J Clin. 2011;61: 91-112.
84. Gridelli C, Maione P, Del Gaizo F, etal. Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer. Oncologist. 2007;12:191-200.
85. Tan EH, Goss GD, Salgia R, etal. Phase 2 trial of Linifanib (ABT-869) in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011;6:1418-1425.
86. Ramalingam SS, Shtivelband M, Soo RA, etal. Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous NSCLC. J Clin Oncol. 2012;30 Suppl:7512.
87. Paz-Ares LG, Biesma B, Heigener D, etal. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012;30:3084-3092.
88. Bria E, Pilotto S, Tortora G. Sorafenib for lung cancer: is the "Battle" still open? Expert Opin Investig Drugs. 2012;21:1445-1448.
89. Zhang J, Gold KA, Kim E. Sorafenib in non-small cell lung cancer. Expert Opin Investig Drugs. 2012;21:1417-1426.
90. Neal JW, Sequist LV. Exciting new targets in lung cancer therapy: ALK, IGF-1R, HDAC, and Hh. Curr Treat Options Oncol. 2010;11: 36-44.
91. Owonikoko TK, Ramalingam SS, Kanterewicz B, Balius TE, Belani CP, Hershberger PA. Vorinostat increases carboplatin and paclitaxel activity in non-small-cell lung cancer cells. Int J Cancer. 2010;126:743-755.
92. Li CT, Hsiao YM, Wu TC, Lin YW, Yeh KT, Ko JL. Vorinostat, SAHA, represses telomerase activity via epigenetic regulation of telomerase reverse transcriptase in non-small cell lung cancer cells. J Cell Biochem. 2011;112:3044-3053.
93. Ouban A, Muraca P, Yeatman T, Coppola D. Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas. Hum Pathol. 2003;34:803-808.
94. Rowinsky EK, Youssoufian H, Tonra JR, Solomon P, Burtrum D, Ludwig DL. IMC-A12, a human IgG1monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res. 2007;13: 5549s-5555s.
95. McKian KP, Haluska P. Cixutumumab. Expert Opin Investig Drugs. 2009;18:1025-1033.
96. Weickhardt A, Doebele R, Oton A, etal. A phase I/II study of erlotinib in combination with the anti-insulin-like growth factor-1 receptor monoclonal antibody IMC-A12 (cixutumumab) in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2012;7:419-426.
97. Scagliotti GV, Novello S. The role of the insulin-like growth factor signaling pathway in non-small cell lung cancer and other solid tumors. Cancer Treat Rev. 2012;38:292-302.
98. Karp DD, Paz-Ares LG, Novello S, etal. Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Oncol. 2009;27:2516-2522.
99. Gualberto A, Hixon ML, Karp DD, etal. Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab. Br J Cancer. 2011;104:68-74.
100. Krysan K, Merchant FH, Zhu L, etal. COX-2-dependent stabilization of survivin in non-small cell lung cancer. FASEB J. 2004;18:206-208.
101. Li F, Liu Y, Chen H, etal. EGFR and COX-2 protein expression in non-small cell lung cancer and the correlation with clinical features. J Exp Clin Cancer Res. 2011;30:27.
102. Tennis MA, Vanscoyk M, Keith RL, Winn RA. The role of prostacyclin in lung cancer. Transl Res. 2010;155:57-61.
103. Mutter R, Lu B, Carbone DP, etal. A phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer. Clin Cancer Res. 2009;15:2158-2165.
104. Mao JT, Roth MD, Fishbein MC, etal. Lung cancer chemoprevention with celecoxib in former smokers. Cancer Prev Res (Phila). 2011;4: 984-993.
105. Cathcart MC, Gray SG, Baird AM, etal. Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer. Cancer. 2011;117:5121-5132.
106. Keith RL, Karoor V, Mozer AB, Hudish TM, Le M, Miller YE. Chemoprevention of murine lung cancer by gefitinib in combination with prostacyclin synthase overexpression. Lung Cancer. 2010;70: 37-42.
107. Keith RL, Miller YE, Hoshikawa Y, etal. Manipulation of pulmonary prostacyclin synthase expression prevents murine lung cancer. Cancer Res. 2002;62:734-740.
108. Nemenoff R, Meyer AM, Hudish TM, etal. Prostacyclin prevents murine lung cancer independent of the membrane receptor by activation of peroxisomal proliferator-activated receptor gamma. Cancer Prev Res (Phila). 2008;1:349-356.
109. Hazra S, Peebles KA, Sharma S, Mao JT, Dubinett SM. The role of PPARgamma in the cyclooxygenase pathway in lung cancer. PPAR Res. 2008;2008:790568.
110. Sasaki H, Tanahashi M, Yukiue H, etal. Decreased perioxisome proliferator-activated receptor gamma gene expression was correlated with poor prognosis in patients with lung cancer. Lung Cancer. 2002;36:71-76.
111. Govindarajan R, Ratnasinghe L, Simmons DL, etal. Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol. 2007;25:1476-1481.
112. Wang M, Zhao J, Zhang LM, etal. Combined erlotinib and cetuximab overcome the acquired resistance to epidermal growth factor receptors tyrosine kinase inhibitor in non-small-cell lung cancer. J Cancer Res Clin Oncol. 2012;138:2069-2077.
113. Haura EB, Tanvetyanon T, Chiappori A, etal. Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:1387-1394.
114. Yamamoto N, Murakami H, Takahashi T, etal. Final results of a Japanese phase 1 trial evaluating a c-met inhibitor tivantinib in combination with an EGFR inhibitor erlotinib in advanced/metastatic non-small cell lung cancer (ARQ 197-003/005 study). Ann Oncol. 2012;23 Suppl 9:ix424.
115. Gridelli C, Morgillo F, Favaretto A, etal. Sorafenib in combination with erlotinib or with gemcitabine in elderly patients with advanced non-small-cell lung cancer: a randomized phase II study. Ann Oncol. 2011;22:1528-1534.
116. Scagliotti GV, Krzakowski M, Szczesna A, etal. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012;30:2070-2078.
117. Van Scoyk M, Randall J, Sergew A, Williams LM, Tennis M, Winn RA. Wnt signaling pathway and lung disease. Transl Res. 2008;151:175-180.
118. Tennis M, Van Scoyk M, Winn RA. Role of the wnt signaling pathway and lung cancer. J Thorac Oncol. 2007;2:889-892.
119. Pacheco-Pinedo EC, Durham AC, Stewart KM, etal. Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium. J Clin Invest. 2011;121:1935-1945.
120. Kim J, You L, Xu Z, etal. Wnt inhibitory factor inhibits lung cancer cell growth. J Thorac Cardiovasc Surg. 2007;133:733-737.
121. Yao H, Ashihara E, Strovel JW, etal. AV-65, a novel Wnt/beta-catenin signal inhibitor, successfully suppresses progression of multiple myeloma in a mouse model. Blood Cancer J. 2011;1:e43.
122. Winn RA, Marek L, Han SY, etal. Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation. J Biol Chem. 2005;280:19625-19634.
123. Tennis MA, Van Scoyk MM, Freeman SV, Vandervest KM, Nemenoff RA, Winn RA. Sprouty-4inhibits transformed cell growth, migration and invasion, and epithelial-mesenchymal transition, and is regulated by Wnt7A through PPARgamma in non-small cell lung cancer. Mol Cancer Res. 2010;8:833-843.
124. Tennis MA, Vanscoyk MM, Wilson LA, Kelley N, Winn RA. Methylation of Wnt7a is modulated by DNMT1 and cigarette smoke condensate in non-small cell lung cancer. PLoS One. 2012;7:e32921.
125. Kaukinen S, Ylitalo P, Pessi T, Vapaatalo H. Hemodynamic effects of iloprost, a prostacyclin analog. Clin Pharmacol Ther. 1984;36:464-469.
126. Tennis MA, Van Scoyk M, Heasley LE, etal. Prostacyclin inhibits non-small cell lung cancer growth by a frizzled 9-dependent pathway that is blocked by secreted frizzled-related protein 1. Neoplasia. 2010;12:244-253.
127. Zhang S, Zhang H, Yang X, etal. Detection of EGFR and KRAS somatic mutations in tumor tissue and peripheral blood by a liquidchip technology for patients with advanced non-small cell lung cancer. J Clin Oncol. 2012;30 Suppl:e18142.
128. Wang K, Stephens P, Yelensky R, etal. Frequency of actionable genomic alterations in early-stage lung adenocarcinoma (LA) detected by next-generation sequencing (NGS). J Clin Oncol. 2012;30 Suppl:e17541.
129. Peifer M, Fernández-Cuesta L, Sos ML, etal. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44:1104-1110.
130. Rudin CM, Durinck S, Stawiski EW, etal. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44:1111-1116.
131. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519-525.