A novel classification of lung cancer into molecular subtypes

PLoS ONE

Volumn 7, Issue 2, 2012, Pages

  West, Lisandra ^a   Vidwans, Smruti J ^a   Campbell, Nicholas P ^b   Shrager, Jeff ^a,c   Simon, George R ^d   Bueno, Raphael ^e   Dennis, Phillip A ^f   Otterson, Gregory A ^g   Salgia, Ravi ^b  

^a Sequoia Consulting   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

^c STANFORD UNIVERSITY   (United States)

^d MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^e BRIGHAM AND WOMEN S HOSPITAL   (United States)

^f NATIONAL CANCER INSTITUTE   (United States)

^g OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 (2,4 DIHYDROXY 5 ISOPROPYLPHENYL) 4 (4 MORPHOLINOMETHYLPHENYL) 3 ISOXAZOLECARBOXYLIC ACID ETHYLAMIDE; ACTIVIN RECEPTOR LIKE KINASE 1; AFATINIB; ANTIBODY; BEVACIZUMAB; CABOZANTINIB; CRIZOTINIB; DACOMITINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; FORETINIB; GANETESPIB; GEFITINIB; HEAT SHOCK PROTEIN 90 INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; MONOCLONAL ANTIBODY; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; PROTEIN TYROSINE KINASE INHIBITOR; RAS PROTEIN; RETASPIMYCIN; RILOTUMUMAB; SCATTER FACTOR; SCATTER FACTOR RECEPTOR; SCATTER FACTOR RECEPTOR ANTIBODY; TIVANTINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN INHIBITOR; XL 765; ANTINEOPLASTIC AGENT;

ADD ON THERAPY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CLASSIFICATION; CANCER RESEARCH; CLINICAL DECISION MAKING; COMBINATION CHEMOTHERAPY; DRUG PROTEIN BINDING; DRUG TARGETING; EGFR GENE; EML4 ALK GENE; FUSION GENE; GENE LOSS; GENETIC DISORDER; HETEROZYGOSITY LOSS; HUMAN; LUNG ADENOCARCINOMA; LUNG CANCER; LUNG NON SMALL CELL CANCER; MET GENE; MISSENSE MUTATION; MOLECULAR TYPING; MUTATIONAL ANALYSIS; ONCOGENE; ONCOGENE K RAS; PATIENT CARE; RECEPTOR BLOCKING; SIGNAL TRANSDUCTION; CELL DEATH; CELL PROLIFERATION; CLASSIFICATION; DRUG EFFECT; GENETICS; LUNG TUMOR; METABOLISM; PATHOLOGY;

ANTINEOPLASTIC AGENTS; CELL DEATH; CELL PROLIFERATION; HUMANS; LUNG NEOPLASMS; MOLECULAR TYPING; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84857410524     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0031906     Document Type: Article

References (100)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, et al. (2011) Global cancer statistics. CA Cancer J Clin 61: 69-90.
2. National Cancer Institute website. Available: http://seer.cancer.gov/statfacts/html/lungb.html. Accessed 2012 Jan 20.
3. Salgia R, Hensing T, Campbell N, Salama AK, Maitland M, et al. (2011) Personalized treatment of lung cancer. Semin Oncol 38: 274-283.
4. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, et al. (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353: 123-132.
5. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, et al. (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361: 947-957.
6. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, et al. (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363: 1693-1703.
7. Vidwans SJ, Flaherty KT, Fisher DE, Tenenbaum JM, Travers MD, et al. (2011) A melanoma molecular disease model. PLoS One 6: e18257.
8. Ludovini V, Bianconi F, Pistola L, Chiari R, Minotti V, et al. (2011) Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. J Thorac Oncol 6: 707-715.
9. Toulany M, Dittmann K, Kruger M, Baumann M, Rodemann HP, (2005) Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother Oncol 76: 143-150.
10. Hanai JI, Doro N, Sasaki AT, Kobayashi S, Cantley LC, et al. (2011) Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-actiated protein kinase (MAPK) and phosphatidylinositol-3- kinase (PI3K)/AKT pathways. J Cell Physiol 227 (4): 1709-1720.
11. Okano J, Gaslightwala I, Birnbaum MJ, Rustgi AK, Nakagawa H, (2000) Akt/protein kinase B isoforms are differentially regulated by epidermal growth factor stimulation. J Biol Chem 275: 30934-30942.
12. Hirsch FR, Scagliotti GV, Langer CJ, Varella-Garcia M, Franklin WA, (2003) Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies. Lung Cancer 41 (Suppl 1): S29-42.
13. National Comprehensive Cancer Network website. Available: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 2012 Jan 20.
14. Mollberg N, Surati M, Demchuk C, Fathi R, Salama AK, et al. (2011) Mind-mapping for lung cancer: towards a personalized therapeutics approach. Adv Ther 28: 173-194.
15. Jackman DM, Miller VA, Cioffredi LA, Yeap BY, Janne PA, et al. (2009) Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res 15: 5267-5273.
16. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, et al. (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362: 2380-2388.
17. Bronte G, Rizzo S, La Paglia L, Adamo V, Siragusa S, et al. (2010) Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma. Cancer Treat Rev 36 (Suppl 3): S21-29.
18. Forbes SA, Bhamra G, Bamford S, Dawson E, Kok C, et al. (2008) The Catalogue of Somatic Mutations in Cancer (COSMIC). Curr Protoc Hum Genet Chapter 10: Unit 10 11.
19. Kosaka T, Yatabe Y, Endoh H, Yoshida K, Hida T, et al. (2006) Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res 12: 5764-5769.
20. Onitsuka T, Uramoto H, Nose N, Takenoyama M, Hanagiri T, et al. (2010) Acquired resistance to gefitinib: the contribution of mechanisms other than the T790M, MET, and HGF status. Lung Cancer 68: 198-203.
21. Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, et al. (2011) 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 17: 1616-1622.
22. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, et al. (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2: e73.
23. Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, et al. (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 105: 2070-2075.
24. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, et al. (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3: 75ra26.
25. Yap TA, Vidal L, Adam J, Stephens P, Spicer J, et al. (2010) Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol 28: 3965-3972.
26. Roushdy-Hammady I, Siegel J, Emri S, Testa JR, Carbone M, (2001) Genetic-susceptibility factor and malignant mesothelioma in the Cappadocian region of Turkey. Lancet 357: 444-445.
27. Cristaudo A, Foddis R, Vivaldi A, Buselli R, Gattini V, et al. (2005) SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study. Cancer Res 65: 3049-3052.
28. Manfredi JJ, Dong J, Liu WJ, Resnick-Silverman L, Qiao R, et al. (2005) Evidence against a role for SV40 in human mesothelioma. Cancer Res 65: 2602-2609.
29. Suda K, Murakami I, Katayama T, Tomizawa K, Osada H, et al. (2010) Reciprocal and complementary role of MET amplification and EGFR T790M mutation in acquired resistance to kinase inhibitors in lung cancer. Clin Cancer Res 16: 5489-5498.
30. Spigel D, Ervin TJ, Ramlau R, Daniel DB, Goldschmidt JH, et al. (2011) Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC. J Clin Oncol 29 (suppl; abstr 7505).
31. Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, et al. (2003) A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425: 407-410.
32. Mosser DD, Morimoto RI, (2004) Molecular chaperones and the stress of oncogenesis. Oncogene 23: 2907-2918.
33. Eccles SA, Massey A, Raynaud FI, Sharp SY, Box G, et al. (2008) NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res 68: 2850-2860.
34. Amann JM, Lee JW, Roder H, Brahmer J, Gonzalez A, et al. (2010) Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in Eastern Cooperative Oncology Group 3503. J Thorac Oncol 5: 169-178.
35. Carbone DP, Salmon JS, Billheimer D, Chen H, Sandler A, et al. (2010) VeriStrat classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab. Lung Cancer 69: 337-340.
36. Chung CH, Seeley EH, Roder H, Grigorieva J, Tsypin M, et al. (2010) Detection of tumor epidermal growth factor receptor pathway dependence by serum mass spectrometry in cancer patients. Cancer Epidemiol Biomarkers Prev 19: 358-365.
37. American Society of Clinical Oncology website. Available: http://www.asco.org/ASCOv2/Practice%26Guidelines/Guidelines/ClinicalPracticeGuidelines/LungCancer. Accessed 2012 Jan 20.
38. Boutin C, Rey F, Gouvernet J, Viallat JR, Astoul P, et al. (1993) Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 2: Prognosis and staging. Cancer 72: 394-404.
39. Sudhir PR, Hsu CL, Wang MJ, Wang YT, Chen YJ, et al. (2011) Phosphoproteomics identifies oncogenic Ras signaling targets and their involvement in lung adenocarcinomas. PLoS One 6: e20199.
40. Bos JL, (1989) ras oncogenes in human cancer: a review. Cancer Res 49: 4682-4689.
41. Quinlan MP, Settleman J, (2009) Isoform-specific ras functions in development and cancer. Future Oncol 5: 105-116.
42. Przybojewska B, Jagiello A, Jalmuzna P, (2000) H-RAS, K-RAS, and N-RAS gene activation in human bladder cancers. Cancer Genet Cytogenet 121: 73-77.
43. Edlundh-Rose E, Egyhazi S, Omholt K, Mansson-Brahme E, Platz A, et al. (2006) NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res 16: 471-478.
44. Goel VK, Lazar AJ, Warneke CL, Redston MS, Haluska FG, (2006) Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma. J Invest Dermatol 126: 154-160.
45. Slebos RJ, Kibbelaar RE, Dalesio O, Kooistra A, Stam J, et al. (1990) K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 323: 561-565.
46. Mascaux C, Iannino N, Martin B, Paesmans M, Berghmans T, et al. (2005) The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 92: 131-139.
47. Ahrendt SA, Decker PA, Alawi EA, Zhu YR, Sanchez-Cespedes M, et al. (2001) Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 92: 1525-1530.
48. Van Damme N, Deron P, Van Roy N, Demetter P, Bols A, et al. (2010) Epidermal growth factor receptor and K-RAS status in two cohorts of squamous cell carcinomas. BMC Cancer 10: 189.
49. Boutin C, Rey F, (1993) Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: Diagnosis. Cancer 72: 389-393.
50. Kelly K, Nawrocki S, Mita A, Coffey M, Giles FJ, et al. (2009) Reovirus-based therapy for cancer. Expert Opin Biol Ther 9: 817-830.
51. National Cancer Institute website. Available: http://www.cancer.gov/cancertopics/druginfo/fda-crizotinib. Accessed 2012 Jan 20.
52. Zhang X, Zhang S, Yang X, Yang J, Zhou Q, et al. (2010) Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer 9: 188.
53. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, et al. (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448: 561-566.
54. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, et al. (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131: 1190-1203.
55. Wong DW, Leung EL, So KK, Tam IY, Sihoe AD, et al. (2009) The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 115: 1723-1733.
56. Takahashi T, Sonobe M, Kobayashi M, Yoshizawa A, Menju T, et al. (2010) Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol 17: 889-897.
57. Butrynski JE, D'Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, et al. (2010) Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 363: 1727-1733.
58. Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, et al. (2009) Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 27: 4247-4253.
59. Heuckmann JM, Holzel M, Sos ML, Heynck S, Balke-Want H, et al. (2011) ALK mutations conferring differential resistance to structurally diverse ALK inhibitors. Clin Cancer Res doi:10.1158/1078-0432.CCR-11-1648.
60. Sattler M, Reddy MM, Hasina R, Gangadhar T, Salgia R, (2011) The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther Adv Med Oncol 3: 171-184.
61. Kim ES, Salgia R, (2009) MET pathway as a therapeutic target. J Thorac Oncol 4: 444-447.
62. Tan YH, Krishnaswamy S, Nandi S, Kanteti R, Vora S, et al. (2010) CBL is frequently altered in lung cancers: its relationship to mutations in MET and EGFR tyrosine kinases. PLoS One 5: e8972.
63. Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, 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: 1479-1488.
64. Kanteti R, Yala S, Ferguson MK, Salgia R, (2009) MET, HGF, EGFR, and PXN gene copy number in lung cancer using DNA extracts from FFPE archival samples and prognostic significance. J Environ Pathol Toxicol Oncol 28: 89-98.
65. Lawrence RE, Salgia R, (2010) MET molecular mechanisms and therapies in lung cancer. Cell Adh Migr 4: 146-152.
66. Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, et al. (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63: 6272-6281.
67. Krishnaswamy S, Kanteti R, Duke-Cohan JS, Loganathan S, Liu W, et al. (2009) Ethnic differences and functional analysis of MET mutations in lung cancer. Clin Cancer Res 15: 5714-5723.
68. Gordon MS, Sweeney CS, Mendelson DS, Eckhardt SG, Anderson A, et al. (2010) Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors. Clin Cancer Res 16: 699-710.
69. Pu X, Hildebrandt MA, Lu C, Lin J, Stewart DJ, et al. (2011) PI3K/PTEN/AKT/mTOR pathway genetic variation predicts toxicity and distant progression in lung cancer patients receiving platinum-based chemotherapy. Lung Cancer 71: 82-88.
70. Al-Saad S, Donnem T, Al-Shibli K, Persson M, Bremnes RM, et al. (2009) Diverse prognostic roles of Akt isoforms, PTEN and PI3K in tumor epithelial cells and stromal compartment in non-small cell lung cancer. Anticancer Res 29: 4175-4183.
71. Yamamoto H, Shigematsu H, Nomura M, Lockwood WW, Sato M, et al. (2008) PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 68: 6913-6921.
72. Jin G, Kim MJ, Jeon HS, Choi JE, Kim DS, et al. (2010) PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers. Lung Cancer 69: 279-283.
73. Pidgeon GP, Barr MP, Harmey JH, Foley DA, Bouchier-Hayes DJ, (2001) Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells. Br J Cancer 85: 273-278.
74. Biroccio A, Candiloro A, Mottolese M, Sapora O, Albini A, et al. (2000) Bcl-2 overexpression and hypoxia synergistically act to modulate vascular endothelial growth factor expression and in vivo angiogenesis in a breast carcinoma line. FASEB J 14: 652-660.
75. Fernandez A, Udagawa T, Schwesinger C, Beecken W, Achilles-Gerte E, et al. (2001) Angiogenic potential of prostate carcinoma cells overexpressing bcl-2. J Natl Cancer Inst 93: 208-213.
76. Iervolino A, Trisciuoglio D, Ribatti D, Candiloro A, Biroccio A, et al. (2002) Bcl-2 overexpression in human melanoma cells increases angiogenesis through VEGF mRNA stabilization and HIF-1-mediated transcriptional activity. FASEB J 16: 1453-1455.
77. Lucchi M, Mussi A, Fontanini G, Faviana P, Ribechini A, et al. (2002) Small cell lung carcinoma (SCLC): the angiogenic phenomenon. Eur J Cardiothorac Surg 21: 1105-1110.
78. Ikegaki N, Katsumata M, Minna J, Tsujimoto Y, (1994) Expression of bcl-2 in small cell lung carcinoma cells. Cancer Res 54: 6-8.
79. 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: 135-138.
80. Stefanaki K, Rontogiannis D, Vamvouka C, Bolioti S, Chaniotis V, et al. (1998) Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas. Anticancer Res 18: 1689-1695.
81. 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: 1035-1042.
82. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, et al. (2005) An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435: 677-681.
83. Tahir SK, Yang X, Anderson MG, Morgan-Lappe SE, Sarthy AV, et al. (2007) Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res 67: 1176-1183.
84. Rudin CM, Hann CL, Peacock CD, Watkins DN, (2008) Novel systemic therapies for small cell lung cancer. J Natl Compr Canc Netw 6: 315-322.
85. Rudin CM, Kozloff M, Hoffman PC, Edelman MJ, Karnauskas R, 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: 1110-1117.
86. Dai Z, Lakshmanan RR, Zhu WG, Smiraglia DJ, Rush LJ, et al. (2001) Global methylation profiling of lung cancer identifies novel methylated genes. Neoplasia 3: 314-323.
87. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, et al. (2002) Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20: 2429-2440.
88. Piekarz RL, Frye R, Turner M, Wright JJ, Allen SL, et al. (2009) Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol 27: 5410-5417.
89. Zhu WG, Lakshmanan RR, Beal MD, Otterson GA, (2001) DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. Cancer Res 61: 1327-1333.
90. Camidge DR, Dziadziuszko R, Hirsch FR, (2009) The rationale and development of therapeutic insulin-like growth factor axis inhibition for lung and other cancers. Clin Lung Cancer 10: 262-272.
91. Nakagawa M, Uramoto H, Oka S, Chikaishi Y, Iwanami T, et al. (2011) Clinical Significance of IGF1R Expression in Non-Small-Cell Lung Cancer. Clin Lung Cancer doi:10.1016/j.cllc.2011.10.006.
92. Kim JS, Kim ES, Liu D, Lee JJ, Solis L, et al. (2011) Prognostic impact of insulin receptor expression on survival of patients with nonsmall cell lung cancer. Cancer doi:10.1002/cncr.26492.
93. Jassem J, Langer CJ, Karp DD, Mok T, Benner RJ, et al. (2010) Randomized, open label, phase III trial of figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). J Clin Oncol 28: abstr 7500.
94. Ramalingam SS, Spigel DR, Chen D, Steins MB, Engelman JA, et al. (2011) Randomized Phase II Study of Erlotinib in Combination With Placebo or R1507, a Monoclonal Antibody to Insulin-Like Growth Factor-1 Receptor, for Advanced-Stage Non-Small-Cell Lung Cancer. J Clin Oncol 29: 4574-4580.
95. Karp DD, Paz-Ares LG, Novello S, Haluska P, Garland L, et al. (2009) Phase II study of the anti-insulin-like growth factor type 1 receptor antibody CP-751,871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non-small-cell lung cancer. J Clin Oncol 27: 2516-2522.
96. Clinicaltrials.gov website. Available: http://clinicaltrials.gov/ct2/show/NCT00887159?term=cixutumumablung&rank=3. Accessed 2012 Jan 20.
97. Clinicaltrials.gov website. Available: http://clinicaltrials.gov/ct2/show/NCT01232452?term=cixutumumablung&rank=6. Accessed 2012 Jan 20.
98. Clinicaltrials.gov website. Available: http://clinicaltrials.gov/ct2/show/NCT01221077?term=osi906lung&rank=2. Accessed 2012 Jan 20.
99. Clinicaltrials.gov website. Available: http://clinicaltrials.gov/ct2/show/NCT01186861?term=osi906lung&rank=3. Accessed 2012 Jan 20.
100. Janku F, Stewart DJ, Kurzrock R, (2010) Targeted therapy in non-small-cell lung cancer-is it becoming a reality? Nat Rev Clin Oncol 7: 401-414.