Rare mutations in non-small-cell lung cancer

Future Oncology

Volumn 9, Issue 5, 2013, Pages 699-711

  D'Arcangelo, Manolo ^a,b   D'Incecco, Armida ^b   Cappuzzo, Federico ^b  

^a UNIVERSITY OF COLORADO   (United States)

^b Livorno Hospital   (Italy)

Author keywords

ALK; BRAF; DDR2; EGFR; gene rearrangement; HER2; mutation; non small cell lung cancer; RET; ROS1

Indexed keywords

B RAF KINASE; CRIZOTINIB; DISCOIDIN; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; FIBROBLAST GROWTH FACTOR RECEPTOR; GEFITINIB; KELCH LIKE ECH ASSOCIATED PROTEIN 1; LAPATINIB; N [3 (5 CHLORO 1H PYRROLO[2,3 B]PYRIDINE 3 CARBONYL) 2,4 DIFLUOROPHENYL]PROPANESULFONAMIDE; PEMETREXED; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN P14; PROTEIN P16; PROTEIN P53; PROTEIN RET; PROTEIN TYROSINE KINASE; SORAFENIB; TRASTUZUMAB; VEMURAFENIB;

AMINO ACID SUBSTITUTION; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER PROGNOSIS; CANCER SURVIVAL; CELL DIFFERENTIATION; CELL PROLIFERATION; CHROMOSOME ABERRATION; COMPUTER ASSISTED EMISSION TOMOGRAPHY; DIMERIZATION; DNA SEQUENCE; EXON; GENE AMPLIFICATION; GENE DELETION; GENE FUSION; GENE MUTATION; GENE REARRANGEMENT; GENE TRANSLOCATION; HISTOLOGY; HUMAN; LIGAND BINDING; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; LUNG SQUAMOUS CELL CARCINOMA; NONHUMAN; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PREDICTIVE VALUE; PREVALENCE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; QUALITY OF LIFE; REAL TIME POLYMERASE CHAIN REACTION; REVIEW; TUMOR XENOGRAFT;

CARCINOMA, NON-SMALL-CELL LUNG; HUMANS; LUNG NEOPLASMS; MOLECULAR TARGETED THERAPY; MUTATION; PROGNOSIS; PROTO-ONCOGENE PROTEINS B-RAF; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2;

EID: 84877623240     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.13.16     Document Type: Review

References (123)

1. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129-2139 (2004).
2. Pao W, Miller V, Zakowsky M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc. Natl Acad. Sci. USA 101, 13306-13311 (2004).
3. Tokumo M, Toyooka S, Kiura K, et al. The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin. Cancer Res. 11, 1167-1173 (2005).
4. Sequist LV, Bell DW, Lynch TJ, Herb DA. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J. Clin. Oncol. 25, 587-595 (2007).
5. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361, 947-957 (2009).
6. Lee JS, Park K, Kim SW, et al. A randomized Phase III study of gefitinib (IRESSA) versus standard chemotherapy (gemcitabine plus cisplatin) as a first-line treatment for never-smokers with advanced or metastatic adenocarcinoma of the lung. J. Thor. Oncol. 4(Suppl. 19), Abstract PRS 4 (2009).
7. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised Phase 3 trial. Lancet Oncol. 11, 121-128 (2010).
8. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 362, 2380-2388 (2010).
9. Zhou CC, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, Phase 3 study. Lancet Oncol. 12, 735-742 (2011).
10. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutations-positive non-small cell lung cancer (EURTAC) a multicenter, open-label, randomized Phase 3 trial. Results of the European Erlotinib Versus Chemotherapy (EURTAC) Phase III randomized trial. Lancet Oncol. 13(3), 239-246 (2012).
11. Marchetti A, Felicioni L, Buttitta F. Assessing EGFR mutations. N. Engl. J. Med. 354(5), 526-528 (2006).
12. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutation in lung cancers. J. Natl Cancer Inst. 97, 339-346 (2005).
13. Perez-Moreno P, Brambilla E, Thomas R, et al. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clin. Cancer Res. 18, 2443-2451 (2012).
14. Kris MG, Johnson BE, Kwiatkowski DJ, et al. 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. 29(Suppl. 15), Abstract CRA7506 (2011).
15. Govindan R, Ding L, Griffith M, et al. Genomic landscape non-small cell lung cancer in smokers and never-smokers. Cell 150, 1121-1134 (2012).
16. Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 13, e23-e31 (2012).
17. Mitsudomi T, Yatabe Y. Mutations of the epidermal growth factor receptor gene and related genes as determinants of the epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer. Cancer Sci. 98, 1817-1824 (2007).
18. Wu JY, Yu CJ, Chang YC, et al. Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small-cell lung cancer. Clin. Cancer Res. 17, 3812-3821 (2011).
19. Ilie MI, Hofman V, Bonnetaud C, et al. Usefullness of tissue microarrays for assessment of protein expression, gene copy number and mutational status of EGFR in lung adenocarcinoma. Virchows Arch. 457, 483-495 (2010).
20. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer-molecular and clinical predictors of outcome. N. Engl. J. Med. 353, 133-144 (2005).
21. De Pas T, Toffalorio F, Manzotti M, et al. Activity of epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations. J. Thorac. Oncol. 6(11), 1895-1901 (2011).
22. He M, Capelletti M, Nafa K, et al. EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma. Clin. Cancer Res. 18, 1790-1797 (2012).
23. Gazdar AF. 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 (2009).
24. Chung KP, Wu SG, Wu JY, et al. Clinical outcomes in non-small cell lung cancer harboring different exon 19 deletions in EGFR. Clin. Cancer Res. 18, 3470-3477 (2012).
25. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat. Rev. Cancer 10, 760-764 (2010).
26. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786-792 (2005).
27. Kobayashi S, Ji H, Yuza Y, et al. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res. 65, 7096-7101 (2005).
28. Cappuzzo F, Ligorio C, Janne PA, et al. Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/ phospho-akt-positive or never smoker patients with advanced non small-cell lung cancer: the ONCOBELL trial. J. Clin. Oncol. 25(16), 2248-2255 (2006).
29. Kosaka T, Yatabe Y, Endoh H, et al. 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 (2006).
30. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2(3), e73 (2005).
31. Balak MN, Gong Y, Riely GJ, et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin. Cancer Res. 12, 6494-6501 (2006).
32. Godin-Heymann N, Bryant I, Rivera MN, et al. Oncogenic activity of epidermal growth factor receptor kinase mutant alleles is enhanced by the T790M drug resistance mutation. Cancer Res. 67, 7319-7326 (2007).
33. Inukai M, Toyooka S, Ito S, et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res. 266, 7854-7858 (2006).
34. Shih JY, Gow CH, Yang PC. EGFR mutation conferring primary resistance to gefitinib in non-small-cell lung cancer. N. Engl. J. Med. 353, 207-208 (2005).
35. Su KY, Chen HY, Li KC, et al. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non small-cell lung cancer. J. Clin. Oncol. 30(4), 433-40 (2012).
36. Fujita Y, Suda K, Kimura H, et al. Highly sensitive detection of EGFR T790M mutation using colony hybridization predicts favorable prognosis of patients with lung cancer harboring activating EGFR mutation. J. Thorac. Oncol. 7(11), 1640-1644 (2012).
37. Rosell R, Molina-Vila MA, Taron M, et al. EGFR compound mutants and survival on erlotinib in non-small cell lung cancer (NSCLC) patients (P) in the EURTAC study. J. Clin. Oncol. 30(Suppl. 15), Abstract 7522 (2012).
38. Rosell R, Molina MA, Costa C, et al. Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clin. Cancer Res. 17(5), 1160-1168 (2011).
39. Hirsch FR, Franklin WA, Veve R, et al. Her2/neu expression in malignant lung tumors. Semin. Oncol. 29, 51-58 (2002).
40. Stephens P, Hunter C, Bignell G, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431(7008), 525-526 (2004).
41. Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 65, 1642-6 (2005).
42. Sequist LV, Heist RS, Shaw AT, et al. SNaPshot genotyping of non-small cell lung cancers (NSCLC) in clinical practice. J. Clin. Oncol. 29(Suppl. 15), Abstract 7518 (2011).
43. Buttitta F, Barassi F, Fresu G, et al. Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. Int. J. Cancer 119, 2586-2591 (2006).
44. Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations and molecular spectrum of ERBB2(HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. Cancer Res. 18(18), 4910-4918 (2012).
45. Tomizawa K, Suda K, Onozato R, et al. Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers. Lung Cancer. 74, 139-44 (2011).
46. Wang SE, Narasanna A, Perez-Torres M, et al. HER2 kinase domain mutation results in constitutivephosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 10, 25-38 (2006).
47. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353, 1673-1684 (2005).
48. Gatzeimeier U, Groth G, Butts C, et al. Randomized Phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann. Oncol. 15, 19-27 (2004).
49. Lara PN, Laptalo L, Longmate J, et al. Trastuzumab plus docetaxel in HER2/neu positive non-small-cell lung cancer: a California Cancer Consortium screening and Phase II trial. Clin. Lung Cancer 5(4), 231-236 (2004).
50. Langer CJ, Stephenson P, Thor A, et al. Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J. Clin. Oncol. 22, 1180-1187 (2004).
51. Zinner RG, Glisson BS, Fossella FV, et al. Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a Phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Lung Cancer 44, 99-110 (2004).
52. Clamon G, Hendon J, Kern J, et al. Lack of activity in non-small cell lung carcinoma with overexpression of erb-B2: 39810: a Phase II trial of cancer and leukemia group B. Cancer 103, 1670-1675 (2005).
53. Scaltriti M, Rojo F, Ocaña A, et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J. Natl Cancer Inst. 99, 628-638 (2007).
54. Cappuzzo F, Cho YG, Sacconi A, et al. p95HER2 truncated form in resected non-small cell lung cancer. J. Thorac. Oncol. 7(3), 520-527 (2012).
55. Cappuzzo F, Bemis L, Varella-Garcia M. HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N. Engl. J. Med. 354(24), 2619-2621 (2006).
56. De Grève J, Teugels E, Geers C, et al. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer 76, 123-127 (2012).
57. Mazieres J, Peters S, Cortot A, et al. Lung cancer harboring HER2 mutation: epidemiological characteristics and therapeutic perspectives. J. Clin. Oncol. 23(Suppl. 9), Abstract 1232PD (2012).
58. Goldberg Z, Kris M, Janne PA, et al. Dacomitinib (PF-00299804), an irreversible pan-HER tyrosine kinase inhibitor (TKI), for first line treatment of EGFR-mutant or HER2-mutant or-amplified lung cancers. Abstract Book of the 37th ESMO Congress. Oxford University Press, Oxford, UK (2012).
59. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 417, 949-954 (2002).
60. Leicht DT, Balan V, Kaplun A, et al. Raf kinases: function, regulation and role in human cancer. Biochim. Biophys. Acta. 1773, 1196-1212 (2007).
61. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct set of genetic alterations in melanoma. N. Engl. J. Med. 353, 2135-2147 (2005).
62. Kimura ET, Nikiforova MN, Zhu Z, et al. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for costitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 63(7), 1454-1457 (2003).
63. Samowitz WS, Sweeney C, Herrick J, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 65, 6063-6069 (2005).
64. Singer G, Oldt R 3rd, Cohen Y, et al. Mutation in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J. Natl Cancer Inst. 95, 484-486 (2003).
65. Brose MS, Volpe P, Feldman M, et al. BRAF and KRAS mutations in human lung cancer and melanoma. Cancer Res. 62, 6997-7000 (2002).
66. Naoki K, Chen TH, Richards WG, et al. Missense mutations of BRAF gene in human lung adenocarcinoma. Cancer Res. 62, 7001-7003 (2002).
67. Sasaki H, Kawano O, Endo K, et al. Uncommon V599E BRAF mutations in Japanese patientswith lung cancer. J. Surg. Res. 133, 203-206 (2006).
68. Pratilas CA, Hanrahan AJ, Halilovic E, et al. Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res. 68, 9375-9383 (2008).
69. Yousem SA, Nikiforova M, Nikiforov Y. The histopathology of BRAF-V600E-mutated lung adenocarcinoma. Am. J. Surg. Pathol. 32, 1317-1321 (2008).
70. Marchetti A, Felicioni L, Malatesta S, et al. Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J. Clin. Oncol. 29, 3574-79 (2011).
71. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl J. Med. 364, 2507-2516 (2011).
72. Zhang XH, Shin JY, Kim JO, et al. Synergistic antitumor efficacy of sequentially combined paclitaxel with sorafenib in vitro and in vivo NSCLC models harboring KRAS or BRAF mutations. Cancer Lett. 322(2), 213-222 (2012).
73. Hanna NH, Pawel JV, Reck M, et al. Carboplatin/paclitaxel with/without sorafenib in chemonaivepatients with stage IIIB-IV non-small-cell lung cancer: interim analysis (IA) results from a randomized Phase III trial (ESCAPE). J. Thor. Oncol. 3(Suppl. 7), Abstract 214 (2008).
74. Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J. Clin. Oncol. 28, 1835-1842 (2010).
75. Paz-Ares L, Hirsh V, Zhang L, et al. Monotherapy administration of sorafenib in patients with non-small cell lung cancer: Phase III, randomized, double-blind, placebo-controlled MISSION trial. Ann. Oncol. 23, Abstract 33 (2012).
76. Gautschi O, Chantal P, Strobel K, et al. A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J. Thor. Oncol. 7(10), e23-e24 (2012).
77. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153), 561-566 (2007).
78. Bai RY, Dieter P, Peschel C, et al. Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity. Mol. Cell Biol. 18(12), 6951-6961 (1998).
79. Chiarle R, Gong JZ, Guasparri I, et al. NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors. Blood 101(5), 1919-1927 (2003).
80. Takeuchi K, Choi YL, Soda M, et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin. Cancer Res. 14(20), 6618-6624 (2008).
81. Takeuchi K, Choi YL, Togashi Y, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin. Cancer Res. 15(9), 3143-3149 (2009).
82. Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population. Clin. Cancer Res. 15(16),5216-5223 (2009).
83. Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a Phase 1 study. Lancet Oncol. 13(10), 1011-1019 (2012).
84. Shaw AT, Kim DW, Nakagawa K, et al. Phase III study of crizotinib versus pemetrexed or docetaxel chemotherapy in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) (PROFILE 1007). Abstract Book of the 37th ESMO Congress. Oxford University Press, Oxford, UK (2012).
85. Acquaviva J, Wong R, Charest A. The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer. Biochim. Biophys. Acta. 1795, 37-52 (2009).
86. El-Deeb IM, Yoo KH, Lee SH. ROS receptor tyrosine kinase: a new potential target for anticancer drugs. Med. Res. Rev. 31(5), 794-818 (2010).
87. Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat. Med. 18(3), 378-381 (2012).
88. Rimkunas VM, Crosby KE, Li D, et al. Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion. Clin. Cancer Res. 18(16), 4449-57 (2012).
89. Charest A, Kheifets V, Park J, et al. Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma. Proc. Natl Acad. Sci. USA 100, 916-921 (2003).
90. Charest A, Wilker EW, McLaughlin ME, et al. ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Res. 66, 7473-7481 (2006).
91. Li C, Fang R, Sun Y, et al. Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers. PLoS One 6, e28204 (2011).
92. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J. Clin. Oncol. 30, 863-870 (2012).
93. Davies KD, Le AT, Theodoro M, et al. Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin. Cancer Res. 18, 4570-4579 (2012).
94. Yasuda H, de Figueiredo-Pontes LL, Kobayashi S, Costa DB. Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer. J. Thorac. Oncol. 7(7), 1086-1090 (2012).
95. Shaw AT, Camidge DR, Engelman JA, et al. Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. J. Clin. Oncol. 30(Suppl. 15), Abstract 7508 (2012).
96. Airaksinen MS, Titievsky A, Saarma M. GDNF family neurotrophic factor signaling: four masters, one servant? Mol. Cell. Neurosci. 13(5), 313-325 (1999).
97. Phay JE, Shah MH. Targeting RET receptor tyrosine kinase activation in cancer. Clin. Cancer Res. 16(24), 5936-5941 (2010).
98. Ju YS, Lee WC, Shin JY, et al. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res. 22(3), 436-445 (2012).
99. Kohno T, Ichikawa H, Totoki Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat. Med. 18(3), 375-377 (2012).
100. Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat. Med. 18(3), 382-384 (2012).
101. Yokota K, Sasaki H, Okuda K, et al. KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung. Oncol. Rep. 28(4), 1187-1192 (2012).
102. Kan Z, Jaiswal BS, Stinson J, et al. Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466, 869-73 (2010).
103. Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190-1203 (2007).
104. Ikeda K, Wang LH, Torres R, et al. Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen. J. Biol. Chem. 277, 19206-19212 (2002).
105. Ali BR, Xu H, Akawi NA, et al. Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients. Hum. Mol. Genet. 19, 2239-2250 (2010).
106. Ford CE, Lau SK, Zhu CQ, Andersson T, Tsao MS, Vogel WF. Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma. Br. J. Cancer 96, 808-814 (2007).
107. Davies H, Hunter C, Smith R, et al. Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res. 65, 7591-7595 (2005).
108. Hammerman PS, Sos ML, Ramos AH, et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 1, 78-89 (2011).
109. Day E, Waters B, Spiegel K, et al. Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur. J. Pharmacol. 599, 44-53(2008).
110. Rekhtman N, Paik PK, Arcila ME, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations. Clin. Cancer Res.18, 1167-1176 (2012).
111. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363, 1693-1703 (2010).
112. Ji H, Zhao X, Yuza Y, et al. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc. Natl Acad. Sci. USA 103, 7817-7822 (2006).
113. Sasaki H, Kawano O, Endo K, Yukiue H, Yano M, Fujii Y. EGFRvIII mutation in lung cancer correlates with increased EGFR copy number. Oncol. Rep. 17, 319-323 (2007).
114. Kawano O, Sasaki H, Endo K, et al. PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer 54, 209-215 (2006).
115. Yamamoto H, Shigematsu H, Nomura M, et al. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res. 68, 6913-6921 (2008).
116. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550-562 (2009).
117. Malanga D, Scrima M, De Marco C, et al. Activating E17K mutation in the gene encoding the protein kinase AKT1 in a subset of squamous cell carcinoma of the lung. Cell Cycle 7, 665-669 (2008).
118. Do H, Salemi R, Murone C, Mitchell PL, Dobrovic A. Rarity ofAKT1 and AKT3 E17K mutations in squamous cell carcinoma of lung. Cell Cycle 9, 4411-4412 (2010).
119. Jin G, Kim MJ, Jeon HS, et al. PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers. Lung Cancer 69, 279-283 (2010).
120. Shibata T, Ohta T, Tong, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc. Natl Acad. Sci. USA 105, 13568-13573 (2008).
121. Singh A, Misra V, Thimmulappa RK, et al. Dysfunctional KEAP1-NRF2 interactions in non-small-cell lung cancer. PLoS Med. 3, e420 (2006).
122. The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489, 519-525 (2012).
123. ClinicalTrials.gov. PF-00299804 as a single oral agent in selected patients with adenocarcinoma of the lung. http://clinicaltrials.gov/ct2/show/ NCT00818441?term=NCT00818441 &rank=1