Epidermal growth factor receptor inhibition in lung cancer: The evolving role of individualized therapy

Cancer and Metastasis Reviews

Volumn 29, Issue 1, 2010, Pages 37-48

  Gazdar, Adi F ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Epidermal growth factor receptor; NSCLC; Resistance; Targeted therapy

Indexed keywords

2 (1H INDAZOL 4 YL) 6 (4 METHANESULFONYL 1 PIPERAZINYLMETHYL) 4 MORPHOLINOTHIENO[3,2 D]PYRIMIDINE; 5 (4 BROMO 2 CHLOROANILINO) 4 FLUORO 1 METHYL 1H BENZIMIDAZOLE 6 CARBOHYDROXAMIC ACID 2 HYDROXYETHYL ESTER; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ANTINEOPLASTIC AGENT; AV 412; BMS 690514; CETUXIMAB; CISPLATIN; DASATINIB; DEFOROLIMUS; ENZASTAURIN; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; EVEROLIMUS; GEFITINIB; ISIS 3521; MATUZUMAB; MP 412; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; N [4 (3 CHLORO 4 FLUOROANILINO) 7 (TETRAHYDRO 3 FURYLOXY) 6 QUINAZOLINYL] 4 DIMETHYLAMINO 2 BUTENAMIDE; NAVELBINE; PANITUMUMAB; PELITINIB; PF 299804; TEMSIROLIMUS; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; XL 147; XL 647; XL 765;

ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; CHEMOTHERAPY INDUCED EMESIS; CLINICAL TRIAL; DIARRHEA; DRUG EFFICACY; DRUG INDICATION; DRUG RESEARCH; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INACTIVATION; ENZYME INHIBITION; FATIGUE; GENE MUTATION; HUMAN; LUNG NON SMALL CELL CANCER; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; RECEPTOR BLOCKING; REVIEW; SIGNAL TRANSDUCTION; SKIN MANIFESTATION; SKIN TOXICITY; TUMOR PROMOTION;

ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG DELIVERY SYSTEMS; HUMANS; INDIVIDUALIZED MEDICINE; LUNG NEOPLASMS; MODELS, BIOLOGICAL; PROTEIN KINASE INHIBITORS; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 77349125581     PISSN: 01677659     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10555-010-9201-z     Document Type: Review

References (111)

1. World Health Organization. (2008). Fact sheet no. 310: the top ten causes of death. November 2008. http://www.who.int/mediacentre/factsheets/fs310-2008. pdf. Accessed 8 Oct 2009.
2. American Cancer Society. (2009). Cancer facts & figures, 2009. Atlanta, GA: American Cancer Society, Inc.
3. National Comprehensive Cancer Network. (2009). NCCN Clinical Practice Guidelines in Oncology™: Non-Small Cell Lung Cancer V.1.2010. http://www.nccn.org/professionals/physician-gls/PDF/nscl.pdf. Accessed 15 Dec 2009.
4. OS Breathnach B Freidlin B Conley MR Green DH Johnson DR Gandara, et al. 2001 Twenty-two years of phase III trials for patients with advanced non-small-cell lung cancer: sobering results Journal of Clinical Oncology 19 6 1734 1742 11251004
5. DN Carney 2002 Lung cancer-time to move on from chemotherapy New England Journal of Medicine 346 2 126 128 10.1056/NEJM200201103460211 11784881 (Pubitemid 34438905)
6. DH Johnson L Fehrenbacher WF Novotny RS Herbst JJ Nemunaitis DM Jablons, et al. 2004 Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer Journal of Clinical Oncology 22 11 2184 2191 10.1200/JCO.2004.11.022 15169807 (Pubitemid 41095154)
7. A Sandler R Gray MC Perry J Brahmer JH Schiller A Dowlati, et al. 2006 Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer New England Journal of Medicine 355 24 2542 2550 10.1056/NEJMoa061884 17167137 (Pubitemid 44917502)
8. M Sibilia R Kroismayr BM Lichtenberger A Natarajan M Hecking M Holcmann 2007 The epidermal growth factor receptor: from development to tumorigenesis Differentiation 75 9 770 787 10.1111/j.1432-0436.2007.00238.x 17999740 (Pubitemid 350086174)
9. D Hanahan RA Weinberg 2000 The hallmarks of cancer Cell 100 1 57 70 10.1016/S0092-8674(00)81683-9 10647931
10. FR Hirsch M Varella-Garcia F Cappuzzo 2009 Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer Oncogene 28 Suppl 1 S32 S37 10.1038/onc.2009.199 19680294
11. FR Hirsch GV Scagliotti CJ Langer M Varella-Garcia WA Franklin 2003 Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies Lung Cancer 41 Suppl 1 S29 S42 10.1016/S0169-5002(03)00137-5 12867060 (Pubitemid 36818993)
12. AF Gazdar 2009 Personalized medicine and inhibition of EGFR signaling in lung cancer New England Journal of Medicine 361 10 1018 1020 10.1056/NEJMe0905763 19692681
13. MV Grandal IH Madshus 2008 Epidermal growth factor receptor and cancer: control of oncogenic signalling by endocytosis Journal of Cellular and Molecular Medicine 12 5A 1527 1534 10.1111/j.1582-4934.2008.00298.x 18318691
14. RS Herbst JV Heymach SM Lippman 2008 Lung cancer New England Journal of Medicine 359 13 1367 1380 10.1056/NEJMra0802714 18815398
15. F Ciardiello G Tortora 2008 EGFR antagonists in cancer treatment New England Journal of Medicine 358 11 1160 1174 10.1056/NEJMra0707704 18337605
16. JJ Laskin AB Sandler 2004 Epidermal growth factor receptor: a promising target in solid tumours Cancer Treatment Reviews 30 1 1 17 10.1016/j.ctrv.2003. 10.002 14766123 (Pubitemid 38240085)
17. C Ho J Laskin 2009 EGFR-directed therapies to treat non-small-cell lung cancer Expert Opinion on Investigational Drugs 18 8 1133 1145 10.1517/13543780903066772 19572809
18. B Solomon M Varella-Garcia DR Camidge 2009 ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer Journal of Thoracic Oncology 4 12 1450 1454 20009909
19. A Milano RV De Iaffaioli F Caponigro 2007 Downstream intracellular effectors of epidermal growth factor receptor as targets for anticancer therapy Expert Opinion on Therapeutic Targets 11 6 771 782 10.1517/14728222.11.6.771 17504015 (Pubitemid 46901396)
20. KM Quesnelle AL Boehm JR Grandis 2007 STAT-mediated EGFR signaling in cancer Journal of Cellular Biochemistry 102 2 311 319 10.1002/jcb.21475 17661350 (Pubitemid 47519405)
21. CM Silva 2004 Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis Oncogene 23 48 8017 8023 10.1038/sj.onc.1208159 15489919 (Pubitemid 39468859)
22. S Modi AD Seidman 2002 An update on epidermal growth factor receptor inhibitors Current Oncology Reports 4 1 47 55 10.1007/s11912-002-0047-6 11734113
23. FR Hirsch M Varella-Garcia PA Bunn Jr MV Di Maria R Veve RM Bremmes, et al. 2003 Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis Journal of Clinical Oncology 21 20 3798 3807 10.1200/JCO.2003.11.069 12953099 (Pubitemid 46606235)
24. Y Ohsaki S Tanno Y Fujita E Toyoshima S Fujiuchi Y Nishigaki, et al. 2000 Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression Oncology Reports 7 3 603 607 10767376
25. T John G Liu MS Tsao 2009 Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors Oncogene 28 Suppl 1 S14 S23 10.1038/onc.2009.197 19680292
26. DA Eberhard G Giaccone BE Johnson 2008 Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting Journal of Clinical Oncology 26 6 983 994 10.1200/JCO.2007.12.9858 18281673
27. FR Hirsch M Varella-Garcia PA Bunn Jr WA Franklin R Dziadziuszko N Thatcher, et al. 2006 Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer Journal of Clinical Oncology 24 31 5034 5042 10.1200/JCO.2006.06.3958 17075123 (Pubitemid 46631407)
28. HS Parra R Cavina F Latteri PA Zucali E Campagnoli E Morenghi, et al. 2004 Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-small-cell lung cancer British Journal of Cancer 91 2 208 212 15187994 (Pubitemid 39037060)
29. R Perez-Soler A Chachoua LA Hammond EK Rowinsky M Huberman D Karp, et al. 2004 Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer Journal of Clinical Oncology 22 16 3238 3247 10.1200/JCO.2004.11.057 15310767 (Pubitemid 41103678)
30. MS Tsao A Sakurada JC Cutz CQ Zhu S Kamel-Reid J Squire, et al. 2005 Erlotinib in lung cancer-molecular and clinical predictors of outcome New England Journal of Medicine 353 2 133 144 10.1056/NEJMoa050736 16014883 (Pubitemid 41058345)
31. RL Rego NR Foster TC Smyrk M Le MJ O'Connell DJ Sargent, et al. 2010 Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status British Journal of Cancer 102 165 172 10.1038/sj.bjc.6605473 19997103
32. J Isola M Tanner A Forsyth TG Cooke AD Watters JM Bartlett 2004 Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization Clinical Cancer Research 10 14 4793 4798 10.1158/1078-0432.CCR-0428-03 15269154 (Pubitemid 38955532)
33. CQ Zhu SG da Cunha K Ding A Sakurada JC Cutz N Liu, et al. 2008 Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21 Journal of Clinical Oncology 26 26 4268 4275 10.1200/JCO.2007.14.8924 18626007
34. FR Hirsch RS Herbst C Olsen K Chansky J Crowley K Kelly, et al. 2008 Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy Journal of Clinical Oncology 26 20 3351 3357 10.1200/JCO.2007.14.0111 18612151
35. FR Hirsch M Varella-Garcia F Cappuzzo J McCoy L Bemis AC Xavier, et al. 2007 Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib Annals of Oncology 18 4 752 760 10.1093/annonc/mdm003 17317677 (Pubitemid 46523281)
36. R Dziadziuszko SE Witta F Cappuzzo S Park K Tanaka PV Danenberg, et al. 2006 Epidermal growth factor receptor messenger RNA expression, gene dosage, and gefitinib sensitivity in non-small cell lung cancer Clinical Cancer Research 12 10 3078 3084 10.1158/1078-0432.CCR-06-0106 16707605 (Pubitemid 43837354)
37. J Gandhi J Zhang Y Xie J Soh H Shigematsu W Zhang, et al. 2009 Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines PLoS ONE 4 2 e4576 10.1371/journal.pone.0004576 19238210
38. DW Bell TJ Lynch SM Haserlat PL Harris RA Okimoto BW Brannigan, et al. 2005 Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials Journal of Clinical Oncology 23 31 8081 8092 10.1200/JCO.2005.02.7078 16204011 (Pubitemid 46657411)
39. R Dziadziuszko B Holm BG Skov K Osterlind MV Sellers WA Franklin, et al. 2007 Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy Annals of Oncology 18 3 447 452 10.1093/annonc/mdl407 17082511 (Pubitemid 46359621)
40. T Takano Y Ohe H Sakamoto K Tsuta Y Matsuno U Tateishi, et al. 2005 Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer Journal of Clinical Oncology 23 28 6829 6837 10.1200/JCO.2005.01.0793 15998907 (Pubitemid 46260269)
41. AF Gazdar 2009 Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors Oncogene 28 Suppl 1 S24 S31 10.1038/onc.2009.198 19680293
42. DB Costa S Kobayashi DG Tenen MS Huberman 2007 Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers Lung Cancer 58 1 95 103 10.1016/j.lungcan.2007.05.017 17610986 (Pubitemid 47379970)
43. A Inoue T Suzuki T Fukuhara M Maemondo Y Kimura N Morikawa, et al. 2006 Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations Journal of Clinical Oncology 24 21 3340 3346 10.1200/JCO.2005.05.4692 16785471 (Pubitemid 46638887)
44. TJ Lynch DW Bell R Sordella S Gurubhagavatula RA Okimoto BW Brannigan, et al. 2004 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib New England Journal of Medicine 350 21 2129 2139 10.1056/NEJMoa040938 15118073 (Pubitemid 38637993)
45. VA Miller GJ Riely MF Zakowski AR Li JD Patel RT Heelan, et al. 2008 Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib Journal of Clinical Oncology 26 9 1472 1478 10.1200/JCO.2007.13.0062 18349398
46. JG Paez PA Janne JC Lee S Tracy H Greulich S Gabriel, et al. 2004 EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy Science 304 5676 1497 1500 10.1126/science.1099314 15118125 (Pubitemid 38720929)
47. W Pao V Miller M Zakowski J Doherty K Politi I Sarkaria, et al. 2004 EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib Proceedings of the National Academy of Sciences of the United States of America 101 36 13306 13311 10.1073/pnas.0405220101 15329413 (Pubitemid 39209661)
48. LV Sequist RG Martins D Spigel SM Grunberg A Spira PA Janne, et al. 2008 First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations Journal of Clinical Oncology 26 15 2442 2449 10.1200/JCO.2007.14.8494 18458038
49. K Tamura I Okamoto T Kashii S Negoro T Hirashima S Kudoh, et al. 2008 Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403) British Journal of Cancer 98 5 907 914 10.1038/sj.bjc.6604249 18283321 (Pubitemid 351341609)
50. M Taron Y Ichinose R Rosell T Mok B Massuti L Zamora, et al. 2005 Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas Clinical Cancer Research 11 16 5878 5885 10.1158/1078-0432.CCR-04-2618 16115929 (Pubitemid 41170316)
51. TS Mok YL Wu S Thongprasert CH Yang DT Chu N Saijo, et al. 2009 Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma New England Journal of Medicine 361 10 947 957 10.1056/NEJMoa0810699 19692680
52. R Rosell T Moran C Queralt R Porta F Cardenal C Camps, et al. 2009 Screening for epidermal growth factor receptor mutations in lung cancer New England Journal of Medicine 361 10 958 967 10.1056/NEJMoa0904554 19692684
53. H Greulich TH Chen W Feng PA Janne JV Alvarez M Zappaterra, et al. 2005 Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants PLoS Medicine 2 11 e313 10.1371/journal.pmed.0020313 16187797 (Pubitemid 41735785)
54. MA Molina-Vila J Bertran-Alamillo N Reguart M Taron E Castella M Llatjos, et al. 2008 A sensitive method for detecting EGFR mutations in non-small cell lung cancer samples with few tumor cells Journal of Thoracic Oncology 3 11 1224 1235 10.1097/JTO.0b013e318189f579 18978556
55. DxS Diagnostic Innovations. (2009). DxS EGFR mutation test kit: for the detection of 29 mutations in the epidermal growth factor receptor (EGFR) gene. Instructions for use. Product codes: EG-03 and EG-04. Instructions Version: RU001b. Date of Revision: July 2009. http://www.dxsdiagnostics.com/Site/PDF/CMP/ RUO-EGFR29/IFU-EGFR29-RUO-US.pdf. Accessed 28 Dec 2009.
56. PC Mack WS Holland RA Burich R Sangha LJ Solis Y Li, et al. 2009 EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer Journal of Thoracic Oncology 4 12 1466 1472 19884861
57. X Zhang A Chang 2008 Molecular predictors of EGFR-TKI sensitivity in advanced non-small cell lung cancer International Journal of Medical Sciences 5 4 209 217 18645621
58. M Ladanyi W Pao 2008 Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond Modern Pathology 21 Suppl 2 S16 S22 10.1038/modpathol.3801018 18437168 (Pubitemid 351592769)
59. NE Hynes HA Lane 2005 ERBB receptors and cancer: the complexity of targeted inhibitors Nature Reviews Cancer 5 5 341 354 10.1038/nrc1609 15864276 (Pubitemid 40637826)
60. J Mendelsohn J Baselga 2003 Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer Journal of Clinical Oncology 21 14 2787 2799 10.1200/JCO.2003.01.504 12860957 (Pubitemid 46606324)
61. K Kelly K Chansky LE Gaspar KS Albain J Jett YC Ung, et al. 2008 Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023 Journal of Clinical Oncology 26 15 2450 2456 10.1200/JCO.2007.14. 4824 18378568
62. U Gatzemeier A Pluzanska A Szczesna E Kaukel J Roubec F De Rosa, et al. 2007 Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial Journal of Clinical Oncology 25 12 1545 1552 10.1200/JCO.2005.05.1474 17442998 (Pubitemid 46733081)
63. R Pirker JR Pereira A Szczesna PJ von Pawel M Krzakowski R Ramlau, et al. 2009 Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial Lancet 373 9674 1525 1531 10.1016/S0140-6736(09)60569-9 19410716
64. Merck KGaA. (2009). News release. November 19, 2009. CHMP opinion for erbitux in advanced non-small cell lung cancer. http://news.merck.de/N/0/ 95F233DCB18F57F1C1257673003661FC/File/CHMP-neg-En.pdf. Accessed 15 Dec 2009.
65. N Thatcher A Chang P Parikh PJ Rodrigues T Ciuleanu PJ van Pawel, et al. 2005 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 366 9496 1527 1537 10.1016/S0140-6736(05)67625-8 16257339 (Pubitemid 41540110)
66. FA Shepherd PJ Rodrigues T Ciuleanu EH Tan V Hirsh S Thongprasert, et al. 2005 Erlotinib in previously treated non-small-cell lung cancer New England Journal of Medicine 353 2 123 132 10.1056/NEJMoa050753 16014882 (Pubitemid 41058344)
67. ® (erlotinib) tablets, oral [package insert]. Melville, NY: OSI Pharmaceuticals Inc. (2009).
68. S Kobayashi TJ Boggon T Dayaram PA Janne O Kocher M Meyerson, et al. 2005 EGFR mutation and resistance of non-small-cell lung cancer to gefitinib New England Journal of Medicine 352 8 786 792 10.1056/NEJMoa044238 15728811 (Pubitemid 40271173)
69. T Kosaka Y Yatabe H Endoh K Yoshida T Hida M Tsuboi, et al. 2006 Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib Clinical Cancer Research 12 19 5764 5769 10.1158/1078-0432.CCR-06-0714 17020982 (Pubitemid 44629607)
70. W Pao VA Miller KA Politi GJ Riely R Somwar MF Zakowski, et al. 2005 Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain PLoS Medicine 2 3 e73 10.1371/journal.pmed.0020073 15737014 (Pubitemid 40629469)
71. DA Eberhard BE Johnson LC Amler AD Goddard SL Heldens RS Herbst, et al. 2005 Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib Journal of Clinical Oncology 23 25 5900 5909 10.1200/JCO.2005.02.857 16043828 (Pubitemid 46300206)
72. W Pao TY Wang GJ Riely VA Miller Q Pan M Ladanyi, et al. 2005 KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib PLoS Medicine 2 1 e17 10.1371/journal.pmed.0020017 15696205 (Pubitemid 40412734)
73. MN Balak Y Gong GJ Riely R Somwar AR Li MF Zakowski, et al. 2006 Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors Clinical Cancer Research 12 21 6494 6501 10.1158/1078-0432.CCR-06- 1570 17085664 (Pubitemid 44799723)
74. K Suda R Onozato Y Yatabe T Mitsudomi 2009 EGFR T790M mutation: a double role in lung cancer cell survival? Journal of Thoracic Oncology 4 1 1 4 19096299
75. S Maheswaran LV Sequist S Nagrath L Ulkus B Brannigan CV Collura, et al. 2008 Detection of mutations in EGFR in circulating lung-cancer cells New England Journal of Medicine 359 4 366 377 10.1056/NEJMoa0800668 18596266
76. J Bean C Brennan JY Shih G Riely A Viale L Wang, et al. 2007 MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib Proceedings of the National Academy of Sciences of the United States of America 104 52 20932 20937 10.1073/pnas.0710370104 18093943
77. M Aita G Fasola C Defferrari A Brianti MG Bello A Follador, et al. 2008 Targeting the VEGF pathway: antiangiogenic strategies in the treatment of non-small cell lung cancer Critical Reviews in Oncology/Hematology 68 3 183 196 10.1016/j.critrevonc.2008.05.002 18606548
78. RH Alvarez HM Kantarjian JE Cortes 2006 Biology of platelet-derived growth factor and its involvement in disease Mayo Clinic Proceedings 81 9 1241 1257 10.4065/81.9.1241 16970222
79. M Guix AC Faber SE Wang MG Olivares Y Song S Qu, et al. 2008 Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins Journal of Clinical Investigation 118 7 2609 2619 18568074
80. SA Kono ME Marshall KE Ware LE Heasley 2009 The fibroblast growth factor receptor signaling pathway as a mediator of intrinsic resistance to EGFR-specific tyrosine kinase inhibitors in non-small cell lung cancer Drug Resistance Updates 12 4-5 95 102 10.1016/j.drup.2009.05.001 19501013
81. EL Kwak R Sordella DW Bell N Godin-Heymann RA Okimoto BW Brannigan, et al. 2005 Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib Proceedings of the National Academy of Sciences of the United States of America 102 21 7665 7670 10.1073/pnas.0502860102 15897464 (Pubitemid 40741028)
82. HA Burris III 2009 Shortcomings of current therapies for non-small-cell lung cancer: unmet medical needs Oncogene 28 Suppl 1 S4 S13 10.1038/onc.2009.196 19680296
83. CD Britten 2004 Targeting ErbB receptor signaling: a pan-ErbB approach to cancer Molecular Cancer Therapeutics 3 10 1335 1342 15486201
84. C-H Yang J-Y Shih W-C Su T-C Hsia C-L Ho AZ Dudek, et al. 2009 BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor, in chemonaïve patients with adenocarcinoma of the lung and activating EGFR mutations (LUX-Lung 2) Journal of Thoracic Oncology 4 9 suppl 1 S294 S295 Abstract A3.3
85. H Xu Y Yu D Marciniak AK Rishi FH Sarkar O Kucuk, et al. 2005 Epidermal growth factor receptor (EGFR)-related protein inhibits multiple members of the EGFR family in colon and breast cancer cells Molecular Cancer Therapeutics 4 3 435 442 15767552
86. D Ye J Mendelsohn Z Fan 1999 Augmentation of a humanized anti-HER2 mAb 4D5 induced growth inhibition by a human-mouse chimeric anti-EGF receptor mAb C225 Oncogene 18 3 731 738 10.1038/sj.onc.1202319 9989823 (Pubitemid 29080330)
87. Shih, J.-Y., Yang, C.-H., Su, W.-C., Hsia, T.-C., Tsia, C.-M., Chen, Y.-M., et al. (2009). A phase II study of BIBW 2992, a novel irreversible dual EGFR and HER2 TKI, in patients with adenocarcinoma of the lung and activating EGFR mutations after failure of one line of chemotherapy (LUX-Lung 2). Journal of Clinical Oncology, 27(suppl), 15S. Abstract 8013.
88. FA Eskens CH Mom AS Planting JA Gietema A Amelsberg H Huisman, et al. 2008 A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours British Journal of Cancer 98 1 80 85 10.1038/sj.bjc.6604108 18026190
89. Yang, C.-H., Shih, J.-Y., Su, W.-C., Hsia, T.-C., Ho, C.-L., Dudek, A. Z., et al. BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor, in chemonaïve patients with adenocarcinoma of the lung and activating EGFR mutations (LUX-Lung 2). Oral presentation at: 13th World Conference on Lung Cancer of the International Association for the Study of Lung Cancer; July 31-August 4, 2009; San Francisco, CA.
90. Shih, J.-Y., Yang, C.-H., Su, W.-C., Hsia, T.-C., Tsai, C.-M., Chen, Y.-M., et al. A phase II study of BIBW 2992, a novel irreversible dual EGFR and HER2 TKI, in patients with adenocarcinoma of the lung and activating EGFR mutations after failure of one line of chemotherapy (LUX-Lung 2). Poster presented at: 45th Annual Meeting of the American Society of Clinical Oncology; May 29-June 2, 2009; Orlando, FL.
91. Yang, C.-H., Hirsh, V., Cadranel, J., Chen, Y.-M., Park, K., Kim, S.-W., et al. Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible, dual inhibitor of EGFR (HER1) and HER2 + BSC versus placebo + BSC in patients with non-small cell lung cancer failing 1-2 lines of chemotherapy and erlotinib or gefitinib (LUX-Lung 1): A preliminary report. Poster presented at: 45th Annual Meeting of the American Society of Clinical Oncology; May 29-June 2, 2009; Orlando, FL.
92. PA Janne K Reckamp M Koczywas DR Camidge JA Engelman F Khuri, et al. 2009 A phase 2 trial of PF-00299804 (PF299), an oral irreversible HER tyrosine kinase inhibitor (TKI), in patients (pts) with advanced NSCLC after failure of prior chemotherapy and erlotinib: Preliminary efficacy and safety results Journal of Thoracic Oncology 4 9 suppl 1 S293 S294 Abstract A3.1
93. Natale, R. B., Thongprasert, S., Greco, F. A., et al. (2009). Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: a randomized, double-blind phase III trial (ZEST). Journal of Clinical Oncology, 27 (suppl), Abstract 8009.
94. De Boer, R., Arrieta, O., Gottfried, M., et al. (2009). Vandetanib plus pemetrexed versus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZEAL). Journal of Clinical Oncology, 27(suppl), 409s Abstract 8010.
95. Herbst, R. S., Sun, Y., Korfee, S., et al. (2009). Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advance non-small cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZODIAC). Journal of Clinical Oncology, 27(suppl), 807s Abstract CRA8003.
96. Bahleda, R., Soria, J. C., Harbison, C. T., et al. (2009). Tumor regression and pharmacodynamic (PD) biomarker validation in non-small cell lung cancer (NSCLC) patients treated with the ErbB/VEGFR inhibitor BMS-690514. Journal of Clinical Oncology, 27(suppl), 431s Abstract 8098.
97. AM Shannon BA Telfer PD Smith M Babur A Logie RW Wilkinson, et al. 2009 The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts Clinical Cancer Research 15 21 6619 6629 10.1158/1078-0432.CCR-08-2958 19843666
98. BB Friday C Yu GK Dy PD Smith L Wang SN Thibodeau, et al. 2008 BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins Cancer Research 68 15 6145 6153 10.1158/0008-5472.CAN-08-1430 18676837
99. SD Barrett AJ Bridges DT Dudley AR Saltiel JH Fergus CM Flamme, et al. 2008 The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901 Bioorganic & Medicinal Chemistry Letters 18 24 6501 6504 10.1016/j.bmcl.2008.10.054
100. C Gridelli P Maione A Rossi 2008 The potential role of mTOR inhibitors in non-small cell lung cancer The Oncologist 13 2 139 147 10.1634/theoncologist. 2007-0171 18305058 (Pubitemid 351342577)
101. MM Mita AC Mita QS Chu EK Rowinsky GJ Fetterly M Goldston, et al. 2008 Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies Journal of Clinical Oncology 26 3 361 367 10.1200/JCO.2007.12.0345 18202410 (Pubitemid 351171685)
102. P Wu T Liu Y Hu 2009 PI3K inhibitors for cancer therapy: what has been achieved so far? Current Medicinal Chemistry 16 8 916 930 10.2174/ 092986709787581905 19275602
103. Y Oh RS Herbst H Burris A Cleverly L Musib M Lahn, et al. 2008 Enzastaurin, an oral serine/threonine kinase inhibitor, as second- or third-line therapy of non-small-cell lung cancer Journal of Clinical Oncology 26 7 1135 1141 10.1200/JCO.2007.14.3685 18309949
104. MA Villalona-Calero P Ritch JA Figueroa GA Otterson R Belt E Dow, et al. 2004 A phase I/II study of LY900003, an antisense inhibitor of protein kinase C-alpha, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer Clinical Cancer Research 10 18 Pt 1 6086 6093 10.1158/1078-0432.CCR-04-0779 15447994 (Pubitemid 39287513)
105. Baselga, J., Rojo, F., Dumez, H. (2005). Phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases: a pharmacokinetic (PK)-pharmacodynamic (PD) study to identify the optimal therapeutic dose regimen. Journal of Clinical Oncology, 23. Abstract 3028.
106. Rizvi, N. A., Kris, M. G., Miller, V. A. (2008). Activity of XL647 in clinically selected NSCLC patients (pts) enriched for the presence of EGFR mutations: results from phase 2. Journal of Clinical Oncology, 26. Abstract 8053.
107. N Yoshimura S Kudoh T Kimura S Mitsuoka K Matsuura K Hirata, et al. 2006 EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with non-small cell lung cancer with acquired resistance to gefitinib Lung Cancer 51 3 363 368 10.1016/j.lungcan.2005.10.006 16364494 (Pubitemid 43265820)
108. T Suzuki A Fujii J Ohya Y Amano Y Kitano D Abe, et al. 2007 Pharmacological characterization of MP-412 (AV-412), a dual epidermal growth factor receptor and ErbB2 tyrosine kinase inhibitor Cancer Science 98 12 1977 1984 10.1111/j.1349-7006.2007.00613.x 17888033 (Pubitemid 350002206)
109. MP Gratacap V Martin MC Valera S Allart C Garcia P Sie, et al. 2009 The new tyrosine-kinase inhibitor and anti-cancer drug dasatinib reversibly affects platelet activation in vitro and in vivo Blood 114 9 1884 1892 10.1182/blood-2009-02-205328 19494352
110. RB Natale D Bodkin R Govindan BG Sleckman NA Rizvi A Capo, et al. 2009 Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase II study Journal of Clinical Oncology 27 15 2523 2529 10.1200/JCO.2008.18.6015 19332730
111. Pirker, R., Szczesna, A., von Pawel, J., et al. (2008). FLEX: a randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Proceedings of the American Society of Clinical Oncology, 26. Abstract 3.