Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Current Drugs and Drug Targets in Non-Small Cell Lung Cancer: Limitations and Opportunities

  • Daga, Aditi (Department of Microbiology, MVM Science College, Saurashtra University) ;
  • Ansari, Afzal (BIT virtual Institute of Bioinformatics (GCRI Node), GSBTM) ;
  • Patel, Shanaya (The Gujarat Cancer & Research Institute) ;
  • Mirza, Sheefa (The Gujarat Cancer & Research Institute) ;
  • Rawal, Rakesh (The Gujarat Cancer & Research Institute) ;
  • Umrania, Valentina (Department of Microbiology, MVM Science College, Saurashtra University)
  • Published : 2015.06.03
Download PDF
⟨ Previous Next ⟩

Abstract

Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

Keywords

References

  1. Alimujiang S, Zhang T, Han ZG, et al (2013). Epidermal growth factor receptor tyrosine kinase inhibitor versus placebo as maintenance therapy for advanced non- small-cell lung cancer: a meta-analysis of randomized controlled trials. Asian Pac J Cancer Prev, 14, 2413-9. https://doi.org/10.7314/APJCP.2013.14.4.2413
  2. Ana Christina GC, Enriqueta F (2013). HER2 driven non-small cell lung cancer (NSCLC): potential therapeutic approaches. Transl Lung Cancer Res, 2, 122-7.
  3. Ancuceanu RV, Istudor V (2004) Pharmacologically active natural compounds for lung cancer. Altern Med Rev, 9, 402-19.
  4. Anish Thomas A, Hassan R (2012) Immunotherapies for nonsmall-cell lung cancer and mesothelioma. Lancet Oncology, 13, 301-10. https://doi.org/10.1016/S1470-2045(12)70126-2
  5. Antonicelli A, Cafarotti S, Indini A, et al (2013). EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation. Int J Med Sci, 10, 320-30. https://doi.org/10.7150/ijms.4609
  6. Arcila ME, Oxnard GR, Nafa K, et al (2011). Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of theT790M mutation using a locked nucleic acid-based assay. Clin Cancer Res, 17, 1169-80. https://doi.org/10.1158/1078-0432.CCR-10-2277
  7. Balak MN, Gong Y, Riely GJ, et al (2006). 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, 6494-501. https://doi.org/10.1158/1078-0432.CCR-06-1570
  8. Bergethon K, Shaw AT, Ou SH, et al (2012). ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol, 30, 863-70. https://doi.org/10.1200/JCO.2011.35.6345
  9. Bethune G, Bethune D, Ridgway N, et al (2010). Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis, 2, 48-51.
  10. Yang C, Shih J, Chao T, et al (2008). Use of BIBW 2992, a novel irreversible EGFR/HER2 TKI, to induce regression in patients with adenocarcinoma of the lung and activating EGFR mutations: Preliminary results of a single-arm phase II clinical trial. J Clin Oncol, 26, [Epub ahead of print].
  11. Cai Y, Sheng ZY, Chen Y, et al (2014) Effect of Withaferin A on A549 cellular proliferation and apoptosis in non-small cell lung cancer. Asian Pac J Cancer Prev, 15, 1711-4. https://doi.org/10.7314/APJCP.2014.15.4.1711
  12. Cao W, Li AW, Ren SX, et al (2014). Efficacy of first-line chemotherapy affects the second-line setting response in patients with advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 15, 6799-804. https://doi.org/10.7314/APJCP.2014.15.16.6799
  13. Cappuzzo F, Marchetti A, Skokan M, et al (2009). Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancerpatients. J Clin Oncol, 27, 1667-74. https://doi.org/10.1200/JCO.2008.19.1635
  14. Cardarella S, Johnson B (2013). The impact of genomic changes on treatment of lung cancer. Am J Respir Crit Care Med, 188, 770-5. https://doi.org/10.1164/rccm.201305-0843PP
  15. Chen S, Flower A, Ritchie A, et al (2010). Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: A systematic review. Lung Cancer, 68, 137-45. https://doi.org/10.1016/j.lungcan.2009.11.008
  16. Choi YL, Takeuchi K, Soda M, et al (2008). Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res, 68, 4971-6. https://doi.org/10.1158/0008-5472.CAN-07-6158
  17. Chou PY, Huang GJ, Pan CH, et al (2011). Trilinolein inhibits proliferation of human non-small cell lung carcinoma A549 through the modulation of PI3K/Akt pathway. Am J Chin Med, 39, 803-15. https://doi.org/10.1142/S0192415X11009214
  18. Cipriani NA, Abidoye OO, Vokes E, et al (2009). MET as a target for treatment of chest tumors. Lung Cancer, 63, 169-79. https://doi.org/10.1016/j.lungcan.2008.06.011
  19. Cooper WA, Lam DC, O’Toole SA, et al (2013). Molecular Biology of Lung Cancer. J Thorac Dis, 5, 479-90.
  20. Cross DA, Ashton SE, Ghiorghiu S, et al (2014). AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov [Epub ahaed of print].
  21. Cufi S, Bonavia R, Vazquez-Martin A, Oliveras-Ferraros C, et al (2013). Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo. Sci Rep, 3, 2459. https://doi.org/10.1038/srep02459
  22. Da Cunha Santos G, Shepherd FA, Tsao MS (2011). EGFR mutations and lung cancer. Annu Rev Pathol, 6, 49-69. https://doi.org/10.1146/annurev-pathol-011110-130206
  23. D'Arcangelo M, D'Incecco A, Cappuzzo FE (2013). Rare mutations in non-small-cell lung cancer. Future Oncol, 9, 699-711. https://doi.org/10.2217/fon.13.16
  24. Datta R, Halder SK, Zhang B. (2013). Role of TGF-${\beta}$ signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells. J Cancer Res Clin Oncol, 139, 563-72. https://doi.org/10.1007/s00432-012-1352-6
  25. Davies KD, Le AT, Theodoro MF, et al (2012). Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res, 18, 4570-9. https://doi.org/10.1158/1078-0432.CCR-12-0550
  26. Di BS, Wei KP, Tian JH, et al (2014). Effectiveness and safety of pemetrexed versus docetaxel as a treatment for advanced non-small cell lung cancer: a systematic review and metaanalysis. Asian Pac J Cancer Prev, 15, 3419-24. https://doi.org/10.7314/APJCP.2014.15.8.3419
  27. Ellison G, Zhu G, Moulis A, et al (2013). EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol, 66, 79-89. https://doi.org/10.1136/jclinpath-2012-201194
  28. Engelman JA, Janne PA (2008) Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res, 14, 2895-9. https://doi.org/10.1158/1078-0432.CCR-07-2248
  29. Ercan D, Zejnullahu K, Yonesaka K, et al (2010). Amplification of EGFR T790M causes resistance to an irreversible EGFR inhibitor. Oncogene, 29, 2346-56. https://doi.org/10.1038/onc.2009.526
  30. Fang H, Lin RY, Sun MX, et al (2014). Efficacy and survivalassociated factors with gefitinib combined with cisplatin and gemcitabine for advanced non- small cell lung cancer. Asian Pac J Cancer Prev, 15, 10967-70.
  31. Gainor JF, Shaw AT (2013). Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. J Clin Oncol, 31, 3987-96. https://doi.org/10.1200/JCO.2012.45.2029
  32. Gandhi L, Janne PA (2012). Crizotinib for ALK-rearranged non-small cell lung cancer: a new targeted therapy for a new target. Clin Cancer Res, 18, 3737-42. https://doi.org/10.1158/1078-0432.CCR-11-2393
  33. Hall RD, Gray JE, Chiappori AA (2013). Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control, 20, 22-31. https://doi.org/10.1177/107327481302000105
  34. Hirschowitz EA, Foody T, Kryscio R (2004). Autologous dendritic cell vaccines for non-small-cell lung cancer. J Clin Oncol, 22, 2808-15. https://doi.org/10.1200/JCO.2004.01.074
  35. Hou ZB, Lu KJ, Wu XL, et al (2014). In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment. Asian Pac J Cancer Prev, 15, 1767-9. https://doi.org/10.7314/APJCP.2014.15.4.1767
  36. Husain H, Rudin CM (2011) ALK-targeted therapy for lung cancer: ready for prime time. Oncology (Williston Park), 25, 597-601.
  37. Ise N, Omi K, Nambara D, et al (2011). Overexpressed HER2 in NSCLC is a possible therapeutic target of EGFR inhibitors. Anticancer Res, 31, 4155-61.
  38. Janne PA, Shaw AT, Pereira JR,et al (2013). Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol, 14, 38-47. https://doi.org/10.1016/S1470-2045(12)70489-8
  39. Jemal A, Siegel R, Ward E, et al (2010). Cancer statistics. CA: Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  40. Jessica M, Matteo GL, Silvia N (2006). MET inhibition in lung cancer. Transl Lung Cancer Res, 2, 23-39.
  41. Jose ST, Viteri S, Molina MA, et al (2013). BRAF mutant nonsmall cell lung cancer and treatment with BRAF inhibitors. Transl Lung Cancer Res, 2, 244-50.
  42. Karachaliou N, Mayo C, Costa C, et al (2013). KRAS Mutations in Lung Cancer. Clin Lung Cancer, 14, 205-14. https://doi.org/10.1016/j.cllc.2012.09.007
  43. Katayama R, Shaw AT, Khan TM, et al (2012). Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med, 4, 120ra17.
  44. Kim H, Yoo SB, Choe JY, et al (2011). Detection of ALK gene rearrangement in non-small cell lung cancer: a comparison of fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression. J Thorac Oncol, 6, 1359-66. https://doi.org/10.1097/JTO.0b013e31821cfc73
  45. Kiziltan HS, Bayir AG, Tastekin D, et al (2014). Outcome of daily cisplatin with thoracic chemoradiotherapy in advanced non-small cell lung cancer patients withcomorbid disorders: a pilot study. Asian Pac J Cancer Prev, 15, 8591-4. https://doi.org/10.7314/APJCP.2014.15.20.8591
  46. Kobayashi S, Boggon TJ, Dayaram T, et al (2005). EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med, 352, 786-92. https://doi.org/10.1056/NEJMoa044238
  47. Kris MG, Johnson BE and Kwiatkowski DJ (2011). 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, [Epub ahead of print].
  48. Kwak EL, Bang YJ, Camidge DR, et al (2010). Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med, 363, 1693-703. https://doi.org/10.1056/NEJMoa1006448
  49. Laurie SA, Miller VA, Grant SC, et al (2005). Phase I study of green tea extract in patients with advanced lung cancer. Cancer Chemother Pharmacol, 55, 33-8. https://doi.org/10.1007/s00280-004-0859-1
  50. Lee JY, Lee YM, Chang GC, et al (2011). Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: theversatile adjuvant for gefitinib therapy. PLoS One, 6, 23756. https://doi.org/10.1371/journal.pone.0023756
  51. Li D, Ambrogio L, Shimamura T, et al (2008). BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene, 27, 4702-11. https://doi.org/10.1038/onc.2008.109
  52. Li Y, Zhang S, Geng JX, et al (2013). Curcumin inhibits human non-small cell lung cancer A549 cell proliferation through regulation of Bcl-2/Bax and cytochrome C. Asian Pac J Cancer Prev, 14, 4599-602. https://doi.org/10.7314/APJCP.2013.14.8.4599
  53. Linardou H, Dahabreh IJ, Kanaloupiti D, et al (2008). Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small cell lung cancer and metastatic colorectal cancer. Lancet Oncol, 9, 962-72. https://doi.org/10.1016/S1470-2045(08)70206-7
  54. Lipson D, Capelletti M, Yelensky R, et al (2012). Identification of New ALK and RET Gene Fusions from Colorectal and Lung Cancer Biopsies. Nature Med, 18, 382-4. https://doi.org/10.1038/nm.2673
  55. Liu LZ, Fang J, Zhou Q, et al (2005). Apigenin inhibits expression of vascular endothelial growth factor and angiogenesis in human lung cancer cells: implication of chemoprevention of lung cancer. Mol Pharmacol, 68, 635-43.
  56. Lu Y, Wei C, Xi Z (2014). Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/${\beta}$-catenin pathway. In vitro Cell Dev Biol Anim, 50, 840-50. https://doi.org/10.1007/s11626-014-9779-5
  57. Ma PC, Maulik G, Christensen J, et al (2003). c-Met: structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev, 22, 309-25. https://doi.org/10.1023/A:1023768811842
  58. Ma PC, Tretiakova MS, MacKinnon AC, et al (2008). Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer, 47, 1025-37. https://doi.org/10.1002/gcc.20604
  59. Ma YC, Li C, Gao F, et al (2014). Epigallocatechin gallate inhibits the growth of human lung cancer by directly targeting the EGFR signaling pathway. Oncol Rep, 31, 1343-9. https://doi.org/10.3892/or.2013.2933
  60. Mao C, Qiu LX, Liao RY, et al (2010). KRAS mutations and resistance to EGFR-TKIs treatment in patients with nonsmall cell lung cancer: a meta-analysis of 22 studies. Lung Cancer, 69, 272-8. https://doi.org/10.1016/j.lungcan.2009.11.020
  61. Marchetti A, Felicioni L, Malatesta S, et al (2011). Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol, 29, 3574-9. https://doi.org/10.1200/JCO.2011.35.9638
  62. Massarelli E, Varella-Garcia M, Tang X, et al (2007). 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, 13, 2890-6. https://doi.org/10.1158/1078-0432.CCR-06-3043
  63. Mateen S, Raina K, Agarwal C, et al (2013). Silibinin synergizes with histone deacetylase and DNA methyltransferase inhibitors in upregulating E-cadherinexpression together with inhibition of migration and invasion of human nonsmall cell lung cancer cells. J Pharmacol Exp Ther, 345, 206-14. https://doi.org/10.1124/jpet.113.203471
  64. Mazieres J, Peters S, Lepage B, et al (2013). Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol, 31, 1997-2003. https://doi.org/10.1200/JCO.2012.45.6095
  65. Miller VA, Wakelee HA, Lara PN, et al (2008). Activity and tolerance of XL647 in NSCLC patients with acquired resistance to EGFR-TKIs: Preliminary results of a phase II trial. J Clin Oncol, 26, 430.
  66. Mok TS, Wu YL, Thongprasert S, et al (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 361, 947-57. https://doi.org/10.1056/NEJMoa0810699
  67. Molina JR, Yang P, Cassivi SD, et al (2008). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc, 83, 584-94. https://doi.org/10.1016/S0025-6196(11)60735-0
  68. Natukula K, Jamil K, Pingali UR, et al (2013). Survival analysis in advanced non small cell lung cancer treated with platinum based chemotherapy incombination with paclitaxel, gemcitabine and etoposide. Asian Pac J Cancer Prev, 14, 4661-6. https://doi.org/10.7314/APJCP.2013.14.8.4661
  69. Ohashi K, Sequist LV, Arcila ME, et al (2012). Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutationsin KRAS, NRAS, or MEK1. Proc Natl Acad Sci U S A, 109, 2127-33. https://doi.org/10.1073/pnas.1203530109
  70. Okuda K, Sasaki H, Yukiue H, et al (2008). Met gene copy number predicts the prognosis for completely resected nonsmall cell lung cancer. Cancer Sci, 99, 2280-5. https://doi.org/10.1111/j.1349-7006.2008.00916.x
  71. Osumi H, Matsusaka S, Shinozaki E, et al (2013). Acquired drug resistance conferred by a KRAS gene mutation following the administration of cetuximab: a case report. BMC Res Notes, 6, 508. https://doi.org/10.1186/1756-0500-6-508
  72. Ou SH, Bartlett CH, Mino-Kenudson M, et al (2012). A Success Story to Usher in the Second Decade of Molecular Targeted Therapy Crizotinib for the Treatment of ALK-Rearranged Non-Small Cell Lung Cancer. Oncologist, 17, 1351-75. https://doi.org/10.1634/theoncologist.2012-0311
  73. Oxnard GR, Binder A, Janne PA (2013). New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol, 31, 1097-104. https://doi.org/10.1200/JCO.2012.42.9829
  74. Paik PK, Arcila ME, Fara M,et al (2011). Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol, 29, 2046-51. https://doi.org/10.1200/JCO.2010.33.1280
  75. Pao W, Girard N (2011). New driver mutations in non-small-cell lung cancer. Lancet Oncol, 12, 175-80. https://doi.org/10.1016/S1470-2045(10)70087-5
  76. Pao W, Miller VA, Politi KA, 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, 73. https://doi.org/10.1371/journal.pmed.0020073
  77. Pao W, Wang TY, Riely GJ, et al (2005). KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med, 2, 17. https://doi.org/10.1371/journal.pmed.0020017
  78. Peter M. K. Westcott, Minh D (2013). The genetics and biology of KRAS in lung cancer. Chin J Cancer, 32, 63-70. https://doi.org/10.5732/cjc.012.10098
  79. Pietanza MC, Lynch TJ, Lara PN, et al (2012). XL647-a multitargeted tyrosine kinase inhibitor: results of a phase II study in subjects with non-small cell lung cancer who have progressed after responding to treatment with either gefitinib or erlotinib. J Thorac Oncol, 7, 219- 226. https://doi.org/10.1097/JTO.0b013e31822eebf9
  80. Riely GJ, Marks J, Pao W (2009). KRAS mutations in non-small cell lung cancer. Proc Am Thorac So, 6, 201-5. https://doi.org/10.1513/pats.200809-107LC
  81. Rikova K, Guo A, Zeng Q, et al (2007). Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell, 131, 1190-203. https://doi.org/10.1016/j.cell.2007.11.025
  82. Robinson KW, Sandler AB (2013). The role of MET receptor tyrosine kinase in non-small cell lung cancer and clinical development of targeted anti-MET agents. Oncologist, 18, 115-22. https://doi.org/10.1634/theoncologist.2012-0262
  83. Robinson MJ, Cobb MH (1997). Mitogen-activated protein kinase pathways. Curr Opin Cell Biol, 9, 180-6. https://doi.org/10.1016/S0955-0674(97)80061-0
  84. Roengvoraphoj M, Tsongalis GJ, Dragnev KH, et al (2013). Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients. Cancer Treat Rev, 39, 839-50. https://doi.org/10.1016/j.ctrv.2013.05.001
  85. Rolfo C, Passiglia F, Castiglia M, et al (2014). ALK and crizotinib: after the honeymoon what else? Resistance mechanisms and new therapies to overcome it. Transl Lung Cancer, [Epub ahead of print].
  86. Samuels Y, Waldman T (2010). Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol, 347, 21-41.
  87. Sarah Declerck, Johan Vansteenkiste (2014). Immunotherapy for lung cancer: ongoing clinical trials. Future Oncol, 10, 91-105. https://doi.org/10.2217/fon.13.166
  88. Sarris EG, Saif MW, Syrigos KN (2012). The biological role of PI3K pathway in lung cancer. Pharmaceuticals (Basel), 5, 1236-64. https://doi.org/10.3390/ph5111236
  89. Sasaki H, Shimizu S, Tani Y, et al (2012). RET expression and detection of KIF5B/RET gene rearrangements in Japanese Lung cancer. Cancer Med, 1, 68-75. https://doi.org/10.1002/cam4.13
  90. Scagliotti GV, Novello S, Schiller JH, et al (2012) A phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, nonsmall- cell lung cancer. Clin Lung Cancer, 13, 391-5. https://doi.org/10.1016/j.cllc.2012.01.003
  91. Scagliotti GV, Selvaggi G, Novello S, et al (2004). The biology of epidermal growth factor receptor in lung cancer. Clin Cancer Res, 10, 4227-4232. https://doi.org/10.1158/1078-0432.CCR-040007
  92. Sequist LV, Besse B, Lynch TJ, et al (2010). Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-smallcell lung cancer. J Clin Oncol, 28, 3076-83. https://doi.org/10.1200/JCO.2009.27.9414
  93. Sequist LV, von Pawel J, Garmey EG, et al (2011). Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol, 29, 3307-15. https://doi.org/10.1200/JCO.2010.34.0570
  94. Sequist LV, Waltman BA, Dias-Santagata D, et al (2011). Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med, 75ra26.
  95. Seto T, Kiura K, Nishio M, et al (2013). CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol, 14, 590-8. https://doi.org/10.1016/S1470-2045(13)70142-6
  96. Shaw AT, Camidge DR, Engelman JA, et al (2012). Clinical activity of crizotinib in advanced non-small cell lung cancer (NSCLC). J Clin Oncol , 30, [Epub ahead of print].
  97. Shaw AT, Mehra R, Kim DW, et al (2013). Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. J Clin Oncol, 31, [Epub ahead of print].
  98. Shaw AT, Solomon B, Kenudson MM (2011). Crizotinib and testing for ALK. J Natl Compr Canc Netw, 9, 1335-1341. https://doi.org/10.6004/jnccn.2011.0115
  99. Shaw AT, Solomon B (2011). Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res, 17, 2081-6. https://doi.org/10.1158/1078-0432.CCR-10-1591
  100. Shaw AT, Yeap BY, Mino-Kenudson M, et al (2009). Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol, 27, 4247-53. https://doi.org/10.1200/JCO.2009.22.6993
  101. Shtivelman E, Hensing T, Simon GR, et al (2014). Molecular pathways and therapeutic targets in lung cancer. Oncotarget, 5, 1392-433. https://doi.org/10.18632/oncotarget.1891
  102. Siegelin MD, Borczuk AC (2014). Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab Invest, 94, 129-37.
  103. Simmons BH, Lee JH, Lalwani K, et al (2012). Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lungadenocarcinoma tumors in Kras(G12D-LSL) mice. Cancer Chemother Pharmacol, 70, 213-20. https://doi.org/10.1007/s00280-012-1899-6
  104. Singh RP, Deep G, Chittezhath M, et al (2006). Effect of silibinin on the growth and progression of primary lung tumors in mice. J Natl Cancer Inst, 98, 846-55. https://doi.org/10.1093/jnci/djj231
  105. Song T, Yu W, Wu SX (2014). Subsequent treatment choices for patients with acquired resistance to EGFR-TKIs in non-small cell lung cancer: restore after a drug holiday or switch to another EGFR-TKI? Asian Pac J Cancer Prev, 15, 205-13. https://doi.org/10.7314/APJCP.2014.15.1.205
  106. Spira A and Ettinger DS (2004). Multidisciplinary management of lung cancer. New England Journal of Medicine, 350, 379-92. https://doi.org/10.1056/NEJMra035536
  107. Suda K, Tomizawa K, Mitsudomi T (2010). Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer Metastasis Rev, 29, 49-60. https://doi.org/10.1007/s10555-010-9209-4
  108. Swanton C, Futreal A, Eisen T (2006). Her2-targeted therapies in non-small cell lung cancer. Clin Cancer Res, 12, 4377-83. https://doi.org/10.1158/1078-0432.CCR-06-0115
  109. Takeuchi K, Choi YL, Togashi Y, et al (2009). KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistrybased diagnostic system for ALK-positive lung cancer. Clin Cancer Res, 15, 3143-9. https://doi.org/10.1158/1078-0432.CCR-08-3248
  110. Takeuchi K, Soda M, Togashi Y, et al (2012). RET, ROS1 and ALK fusions in lung cancer. Nature Med, 18, 378-81. https://doi.org/10.1038/nm.2658
  111. Travis WD, Brambilla E, Noguchi M, et al (2011). International association for the study of lung cancer/american thoracic society/european respi¬ratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 6, 244-85. https://doi.org/10.1097/JTO.0b013e318206a221
  112. Ulasli SS, Celik S, Gunay E, et al (2013). Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lungcancer cells exposed to benzo(a) pyrene. Asian Pac J Cancer Prev, 14, 6159-64. https://doi.org/10.7314/APJCP.2013.14.10.6159
  113. Usuda K, Sagawa M, Motono N, et al (2014). Relationships between EGFR mutation status of lung cancer and preoperative factors-are they predictive? Asian Pac J Cancer Prev, 15, 657-62. https://doi.org/10.7314/APJCP.2014.15.2.657
  114. Walter AO, Tjin R, Haringsma H, et al (2011). CO-1686, an orally available, mutant-selective inhibitor of the epidermal growth factor receptor (EGFR), causes tumor shrinkage in non-small cell lung cancer (NSCLC) with T790M resistance mutations. Mol Cancer Ther, 10.
  115. Wang H, Wu H, Cai K, et al (2012). Phosphatidylinositol 3-kinase could be a promising target in lung cancer therapy. J BUON, 17, 729-34.
  116. Wang JY and Cai Y (2013). Clinical observation and prognostic analysis of pemetrexed plus platinum as first-line treatment in patients withadvanced non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 6267-71. https://doi.org/10.7314/APJCP.2013.14.11.6267
  117. Winter H, van den Engel NK, Rusan M, et al (2011). Activespecific immunotherapy for non-small cell lung cancer. J Thorac Dis, 3, 105-14.
  118. Wong KK, Fracasso PM, Bukowski RM, et al (2009). A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res, 15, 2552-8. https://doi.org/10.1158/1078-0432.CCR-08-1978
  119. Yamamoto H, Shigematsu H, Nomura M, et al (2008). PIK3CA mutations and copy number gains in human lung cancers. Cancer Res, 68, 6913-21. https://doi.org/10.1158/0008-5472.CAN-07-5084
  120. Zhang Z, Stiegler AL, Boggon TJ,et al (2010). EGFR-mutated lung cancer: a paradigm of molecular oncology. Oncotarget, 1, 497-514. https://doi.org/10.18632/oncotarget.186
  121. Zou ZQ, Zhang LN, Wang F, et al (2012). The novel dual PI3K/ mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lungcancer cells. Mol Med Rep, 5, 503-8.

Cited by

  1. The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC) vol.95, pp.50, 2016, https://doi.org/10.1097/MD.0000000000005599
  2. Cytokine-induced killer cell therapy for modulating regulatory T cells in patients with non-small cell lung cancer vol.14, pp.1, 2017, https://doi.org/10.3892/etm.2017.4562
  3. DDA1, a novel oncogene, promotes lung cancer progression through regulation of cell cycle vol.21, pp.8, 2017, https://doi.org/10.1111/jcmm.13084
  4. Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy vol.39, pp.3, 2017, https://doi.org/10.1177/1010428317695915
  5. Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-34018-1
  6. Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance vol.10, pp.7, 2018, https://doi.org/10.3390/cancers10070224