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Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

  • Zheng, De-Jie (Department of Clinical Oncology, Weifang People's Hospital) ;
  • Yu, Guo-Hua (Department of Clinical Oncology, Weifang People's Hospital) ;
  • Gao, Jian-Feng (Department of Clinical Oncology, Weifang People's Hospital) ;
  • Gu, Jun-Dong (Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital)
  • Published : 2013.08.30

Abstract

Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

Keywords

Non-small cell lung carcinoma;epidermal growth factor receptor;radiation;combine therapy

References

  1. Koh PK, Faivre-Finn C, Blackhall FH, De Ruysscher D (2012). Targeted agents in non-small cell lung cancer (NSCLC): clinical developments and rationale for the combination with thoracic radiotherapy. Cancer Treat Rev, 38, 626-40 https://doi.org/10.1016/j.ctrv.2011.11.003
  2. Kokubo Y, Gemma A, Noro R, et al (2005). Reduction of PTEN protein and loss of epidermal growth factor receptor gene mutation in lung cancer with natural resistance to gefitinib (IRESSA). Br J Cancer, 92, 1711-9. https://doi.org/10.1038/sj.bjc.6602559
  3. Lammering G, Hewit TH, Valerie K, et al (2003). EGFRvIII-mediated radioresistance through a strong cytoprotective response. Oncogene, 22, 5545-53. https://doi.org/10.1038/sj.onc.1206788
  4. Lammering G, Hewit TH, Holmes M, et al (2004). Inhibition of the type III epidermal growth factor receptor variant mutant receptor by dominant-negative EGFR-CD533 enhances malignant glioma cell radio sensitivity. Clin Cancer Res, 10, 6732-43 https://doi.org/10.1158/1078-0432.CCR-04-0393
  5. Lammering G, Valerie K, Lin PS, et al (2004). Radiation-induced activation of a common variant of EGFR confers enhanced radio resistance. Radiother Oncol, 72, 267-73. https://doi.org/10.1016/j.radonc.2004.07.004
  6. Li C, Iida M, Dunn EF, et al (2010). Dasatinib blocks cetuximab-and radiation-induced nuclear translocation of the epidermal growth factor receptor in head and neck squamous cell carcinoma. Radiother Oncol, 97, 330-7. https://doi.org/10.1016/j.radonc.2010.06.010
  7. Li C, Iida M, Dunn EF, et al (2009). Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene, 28, 3801-13 https://doi.org/10.1038/onc.2009.234
  8. Li J, Yen C, Liaw D, et al (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275, 1943-7. https://doi.org/10.1126/science.275.5308.1943
  9. Liang K, Ang KK, Milas L, et al (2003). The epidermal growth factor receptor mediates radioresistance. Int J Radiat Oncol Biol Phys, 57, 246-54. https://doi.org/10.1016/S0360-3016(03)00511-X
  10. Liao HJ, Carpenter G (2009). Cetuximab/C225-induced intracellular trafficking of epidermal growth factor receptor. Cancer Res, 69, 6179-83. https://doi.org/10.1158/0008-5472.CAN-09-0049
  11. Liccardi G, Hartley JA, Hochhauser D (2011). EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment. Cancer Res, 71, 1103-14 https://doi.org/10.1158/0008-5472.CAN-10-2384
  12. Liotta LA, Kohn EC (2001). The microenvironment of the tumour-host interface. Nature, 411, 375-9. https://doi.org/10.1038/35077241
  13. Lo HW (2010). Nuclear mode of the EGFR signaling network: biology, prognostic value, andtherapeutic implications. Discov Med, 10, 44-51.
  14. Lo HW, Hung MC (2006). Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycleprogression, nitric oxide pathway and patient survival. Br J Cancer, 94, 184-8 https://doi.org/10.1038/sj.bjc.6602941
  15. Lo HW, Xia W, Wei Y, et al (2005). Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res, 65, 338-48.
  16. Lynch TJ, Fenton D, Hirsh V, et al (2009). A randomized phase 2 study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer. J Thorac Oncol, 4, 1002-9 https://doi.org/10.1097/JTO.0b013e3181aba89f
  17. Hirata A, Ogawa S, Kometani T, et al (2002). ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermalgrowth factor receptor tyrosine kinase. Cancer Res, 62, 2554-60.
  18. Hirata A, Uehara H, Izumi K, et al (2004). Direct inhibition of EGF receptor activation in vascular endothelial cells bygefitinib ('Iressa', ZD1839). Cancer Sci, 95, 614-8. https://doi.org/10.1111/j.1349-7006.2004.tb02496.x
  19. Hoshino M, Fukui H, Ono Y, et al (2007). Nuclear expression of phosphorylated EGFR is associated with poor prognosis ofpatients with esophageal squamous cell carcinoma. Pathobiology, 74, 15-21. https://doi.org/10.1159/000101047
  20. Huang SM, Harari PM (2000). Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res, 6, 2166-74.
  21. Jain RK (2005). Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science, 307, 58-62. https://doi.org/10.1126/science.1104819
  22. Janmaat ML, Giaccone G (2003). The epidermal growth factor receptor pathway and its inhibition as anticancer therapy. Drugs Today (Barc), 39, 61-80. https://doi.org/10.1358/dot.2003.39.1.799432
  23. Jemal A, Siegel R, Ward E, et al (2009). Cancer statistics, 2009. CA Cancer J Clin, 59, 225-49. https://doi.org/10.3322/caac.20006
  24. Ji H, Zhao X, Yuza Y, et al (2006). Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci U S A, 103, 7817-22. https://doi.org/10.1073/pnas.0510284103
  25. Jiang BH, Jiang G, Zheng JZ, et al (2001). Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-induciblefactor 1. Cell Growth Differ, 12, 363-9.
  26. Jiang XD, Dai P, Wu J, et al (2012). Effect of recombinant human endostatin on radiosensitivity in patients withnon-small-cell lung cancer. Int J Radiat Oncol Biol Phys, 83, 1272-7 https://doi.org/10.1016/j.ijrobp.2011.09.050
  27. Jiang XD, Dai P, Wu J, et al (2011). Inhibitory effect of radiotherapy combined with weekly recombinant human endostatin on the human pulmonary adenocarcinoma A549 xenografts in nude mice. Lung Cancer, 72, 165-71 https://doi.org/10.1016/j.lungcan.2010.09.003
  28. Jung IL, Kang HJ, Kim KC, Kim IG (2010). PTEN/pAkt/p53 signaling pathway correlates with the radioresponse of non-smallcell lung cancer. Int J Mol Med, 25, 517-23.
  29. Karamouzis MV, Grandis JR, Argiris A (2007). Therapies directed against epidermal growth factor receptor in aerodigestivecarcinomas. JAMA, 298, 70-82. https://doi.org/10.1001/jama.298.1.70
  30. Karar J, Maity A (2011). PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci, 4, 51.
  31. Kim HP, Yoon YK, Kim JW, et al (2009). Lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, downregulates thymidylate synthase by inhibiting the nuclear translocation of EGFR and HER2. PloS One, 4, e5933 https://doi.org/10.1371/journal.pone.0005933
  32. 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
  33. Dittmann K, Mayer C, Fehrenbacher B, et al (2005). Radiation-induced epidermal growth factor receptor nuclear import is linked toactivation of DNA-dependent protein kinase. J Biol Chem, 280, 31182-9. https://doi.org/10.1074/jbc.M506591200
  34. Dittmann K, Mayer C, Rodemann HP (2005). Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol, 76, 157-61. https://doi.org/10.1016/j.radonc.2005.06.022
  35. Dittmann K, Mayer C, Rodemann HP (2010). Nuclear EGFR as novel therapeutic target: insights into nuclear translocation andfunction. Strahlenther Onkol, 186, 1-6.
  36. Endoh H, Yatabe Y, Kosaka T, Kuwano H, Mitsudomi T (2006). PTEN and PIK3CA expression is associated with prolonged survival after gefitinib treatment in EGFR-mutated lung cancer patients. J Thorac Oncol, 1, 629-34. https://doi.org/10.1097/01243894-200609000-00006
  37. Engelman JA, Zejnullahu K, Mitsudomi T, et al (2007). MET amplification leads to gefitinib resistance in lung cancer by activatingERBB3 signaling. Science, 316, 1039-43. https://doi.org/10.1126/science.1141478
  38. Ettinger DS (2006). Clinical implications of EGFR expression in the development and progression of solid tumors: focus on non-small cell lung cancer. Oncologist, 11, 358-73. https://doi.org/10.1634/theoncologist.11-4-358
  39. Franovic A, Gunaratnam L, Smith K, et al (2007). Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutationalexplanation for its overexpression in human cancer. Proc Natl Acad Sci U S A, 104, 13092-7. https://doi.org/10.1073/pnas.0702387104
  40. Garcia-Cao I, Song MS, Hobbs RM, et al (2012). Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell, 149, 49-62. https://doi.org/10.1016/j.cell.2012.02.030
  41. Gupta AK, Bakanauskas VJ, Cerniglia GJ, et al (2001). The Ras radiation resistance pathway. Cancer Res, 61,4278-82.
  42. Han W, Lo HW (2012). Landscape of EGFR signaling network in human cancers: biology and therapeutic response in relation to receptor sub-cellular locations. Cancer Lett, 318, 124-34. https://doi.org/10.1016/j.canlet.2012.01.011
  43. Bonner JA, Harari PM, Giralt J, et al (2006). Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med, 354, 567-78. https://doi.org/10.1056/NEJMoa053422
  44. Bouali S, Chretien AS, Ramacci C, et al (2009). P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab. Cancer Gene Ther, 16, 498-507. https://doi.org/10.1038/cgt.2008.100
  45. Burger JA, Kipps TJ (2006). CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood, 107, 1761-7. https://doi.org/10.1182/blood-2005-08-3182
  46. Cao Y, Langer R (2008). A review of Judah Folkman’s remarkable achievements in biomedicine. Proc Natl Acad Sci U S A, 105, 13203-5. https://doi.org/10.1073/pnas.0806582105
  47. Castellino RC, Durden DL (2007). Mechanisms of disease: the PI3K-Akt-PTEN signaling node--an intercept point forthe control of angiogenesis in brain tumors. Nat Clin Pract Neurol, 3, 682-93.
  48. Cerniglia GJ, Pore N, Tsai JH, et al (2009). Epidermal growth factor receptor inhibition modulates the microenvironment byvascular normalization to improve chemotherapy and radiotherapy efficacy. PloS One, 4, e6539. https://doi.org/10.1371/journal.pone.0006539
  49. Chen DJ, Nirodi CS (2007). The epidermal growth factor receptor: a role in repair of radiation-induced DNA damage. Clin Cancer Res, 13, 6555-60. https://doi.org/10.1158/1078-0432.CCR-07-1610
  50. Christofk HR, Vander HMG, Harris MH, et al (2008). The M2 splice isoform of pyruvate kinase is important for cancer metabolism andtumour growth. Nature, 452, 230-3. https://doi.org/10.1038/nature06734
  51. Chung TD, Broaddus WC (2005). Molecular targeting in radiotherapy: epidermal growth factor receptor. Mol Interv, 5, 15-9. https://doi.org/10.1124/mi.5.1.5
  52. Das AK, Sato M, Story MD, et al (2006). Non-small-cell lung cancers with kinase domain mutations in the epidermal growth factor receptor are sensitive to ionizing radiation. Cancer Res, 66, 9601-8. https://doi.org/10.1158/0008-5472.CAN-06-2627
  53. Das AK, Chen BP, Story MD, et al (2007). Somatic mutations in the tyrosine kinase domain of epidermal growth factorreceptor (EGFR) abrogate EGFR-mediated radioprotection in non-small cell lungcarcinoma. Cancer Res, 67, 5267-74. https://doi.org/10.1158/0008-5472.CAN-07-0242
  54. Debucquoy A, Machiels JP, McBride WH, Haustermans K (2010). Integration of epidermal growth factor receptor inhibitors with preoperativechemoradiation. Clin Cancer Res, 16, 2709-14. https://doi.org/10.1158/1078-0432.CCR-09-1622
  55. Abdollahi A, Hlatky L, Huber PE (2005). Endostatin: the logic of antiangiogenic therapy. Drug Resist Updat, 8, 59-74. https://doi.org/10.1016/j.drup.2005.03.001
  56. An SJ, Chen ZH, Su J, et al (2012). Identification of Enriched Driver Gene Alterations in Subgroups of Non-Small Cell Lung Cancer Patients Based on Histology and Smoking Status. PloS One, 7, e40109. https://doi.org/10.1371/journal.pone.0040109
  57. Lynch TJ, Bell DW, Sordella R, et al (2004). Activating mutations in the epidermal growth factor receptor underlyingresponsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med, 350, 2129-39. https://doi.org/10.1056/NEJMoa040938
  58. Maemondo M, Inoue A, Kobayashi K, et al (2010). Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med, 362, 2380-8. https://doi.org/10.1056/NEJMoa0909530
  59. Maity A, Pore N, Lee J, et al (2000). Epidermal growth factor receptor transcriptionally up-regulates vascularendothelial growth factor expression in human glioblastoma cells via a pathwayinvolving phosphatidylinositol 3’-kinase and distinct from that induced byhypoxia. Cancer Res, 60, 5879-86.
  60. Mak RH, Doran E, Muzikansky A, et al (2011). Outcomes after combined modality therapy for EGFR-mutant and wild-type locallyadvanced NSCLC. Oncologist, 16, 886-95. https://doi.org/10.1634/theoncologist.2011-0040
  61. McKenna WG, Muschel RJ (2003). Targeting tumor cells by enhancing radiation sensitivity. Genes Chromosomes Cancer, 38, 330-8. https://doi.org/10.1002/gcc.10296
  62. Meert AP, Martin B, Delmotte P, et al (2002). The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J, 20, 975-81. https://doi.org/10.1183/09031936.02.00296502
  63. Meyn RE, Munshi A, Haymach JV, et al (2009). Receptor signaling as a regulatory mechanism of DNA repair. Radiother Oncol, 92, 316-22. https://doi.org/10.1016/j.radonc.2009.06.031
  64. Milosevic M, Fyles A, Hedley D, et al (2004). The human tumor microenvironment: invasive (needle) measurement of oxygen and interstitial fluid pressure. Semin Radiat Oncol, 14, 249-58. https://doi.org/10.1016/j.semradonc.2004.04.006
  65. Minjgee M, Toulany M, Kehlbach R, et al (2011). K-RAS(V12) induces autocrine production of EGFR ligands and mediates radioresistance through EGFR-dependent Akt signaling and activation of DNA-PKcs. Int J Radiat Oncol Biol Phys, 81, 1506-14. https://doi.org/10.1016/j.ijrobp.2011.05.057
  66. Mitsudomi T, Morita S, Yatabe Y, et al (2010). 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, randomized phase 3 trial. Lancet Oncol, 11, 121-8. https://doi.org/10.1016/S1470-2045(09)70364-X
  67. 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
  68. Morgan S, Grandis JR (2009). ErbB receptors in the biology and pathology of the aerodigestive tract. Exp Cell Res, 315, 572-82. https://doi.org/10.1016/j.yexcr.2008.08.009
  69. Mukherjee B, McEllin B, Camacho CV, et al (2009). EGFRvIII and DNA double-strand break repair: a molecular mechanism for radioresistance in glioblastoma. Cancer Res, 69, 4252-9. https://doi.org/10.1158/0008-5472.CAN-08-4853
  70. Nicholson RI, Gee JM, Harper ME (2001). EGFR and cancer prognosis. Eur J Cancer, 37, S9-15.
  71. O’Byrne KJ, Danson S, Dunlop D, et al (2007). Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non small-cell lung cancer. J Clin Oncol, 25, 3266-73. https://doi.org/10.1200/JCO.2006.09.2791
  72. Okamoto I, Kenyon LC, Emlet DR, et al (2003). Expression of constitutively activated EGFRvIII in non-small cell lung cancer. Cancer Sci, 94, 50-6. https://doi.org/10.1111/j.1349-7006.2003.tb01351.x
  73. Pao W, Wang TY, Riely GJ, et al (2005). KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med, 2, e17. https://doi.org/10.1371/journal.pmed.0020017
  74. Peng XH, Karna P, Cao Z, et al (2006). Cross-talk between epidermal growth factor receptor and hypoxia-induciblefactor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem, 281, 25903-14. https://doi.org/10.1074/jbc.M603414200
  75. Pollard JW (2004). Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer, 4, 71-8. https://doi.org/10.1038/nrc1256
  76. Pore N, Jiang Z, Gupta A, et al (2006). EGFR tyrosine kinase inhibitors decrease VEGF expression by bothhypoxia-inducible factor (HIF)-1-independent and HIF-1-dependent mechanisms. Cancer Res, 66, 3197-204. https://doi.org/10.1158/0008-5472.CAN-05-3090
  77. Rodemann HP, Dittmann K, Toulany M (2007). Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol, 83, 781-91 https://doi.org/10.1080/09553000701769970
  78. Sasaki H, Kawano O, Endo K, et al (2007). EGFRvIII mutation in lung cancer correlates with increased EGFR copy number. Oncol Rep, 17, 319-23.
  79. Schuurbiers OC, Kaanders JH, der Heijden HF v, et al (2009). The PI3-K/AKT-pathway and radiation resistance mechanisms in non-small cell lung cancer. J Thorac Oncol, 4, 761-7. https://doi.org/10.1097/JTO.0b013e3181a1084f
  80. Semenza GL (2012). Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci, 33, 207-14. https://doi.org/10.1016/j.tips.2012.01.005
  81. Semenza GL (2003). Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 3, 721-32. https://doi.org/10.1038/nrc1187
  82. Sherwood LM, Parris EE, Folkman J (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med, 285, 1182-6. https://doi.org/10.1056/NEJM197111182852108
  83. Shigematsu H, Lin L, Takahashi T, et al (2005). Clinical and biological features associated with epidermal growth factor receptorgene mutations in lung cancers. J Natl Cancer Inst, 97, 339-46. https://doi.org/10.1093/jnci/dji055
  84. Sok JC, Coppelli FM, Thomas SM, et al (2006). Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res, 12, 5064-73 https://doi.org/10.1158/1078-0432.CCR-06-0913
  85. Solomon B, Hagekyriakou J, Trivett MK, et al (2003). EGFR blockade with ZD1839 ("Iressa") potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cellcarcinoma. Epidermal growth factor receptor. Int J Radiat Oncol Biol Phys, 55, 713-23. https://doi.org/10.1016/S0360-3016(02)04357-2
  86. Sos ML, Koker M, Weir BA, et al (2009). PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res, 69, 3256-61. https://doi.org/10.1158/0008-5472.CAN-08-4055
  87. Stambolic V, MacPherson D, Sas D, et al (2001). Regulation of PTEN transcription by p53. Mol Cell, 8, 317-25. https://doi.org/10.1016/S1097-2765(01)00323-9
  88. Tang Y, Eng C (2006). PTEN autoregulates its expression by stabilization of p53 in aphosphatase-independent manner. Cancer Res, 66, 736-42. https://doi.org/10.1158/0008-5472.CAN-05-1557
  89. Tomioka A, Tanaka M, De Velasco MA, et al (2008). Delivery of PTEN via a novel gene microcapsule sensitizes prostate cancer cellsto irradiation. Mol Cancer Ther, 7, 1864-70 https://doi.org/10.1158/1535-7163.MCT-07-2198
  90. Toulany M, Baumann M, Rodemann HP (2003). Stimulated PI3K-AKT signaling mediated through ligand or radiation-induced EGFRdepends indirectly, but not directly, on constitutive K-Ras activity. Mol Cancer Res, 5, 863-72.
  91. Toulany M, Dittmann K, Kruger M, et al (2005). Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother Oncol, 76, 143-50. https://doi.org/10.1016/j.radonc.2005.06.024
  92. Wang J, Ouyang W, Li J, et al (2005). Loss of tumor suppressor p53 decreases PTEN expression and enhances signaling pathways leading to activation of activator protein 1 and nuclear factor kappaBinduced by UV radiation. Cancer Res, 65, 6601-11. https://doi.org/10.1158/0008-5472.CAN-04-4184
  93. Wang X, Schneider A (2010). HIF-2alpha-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia. Carcinogenesis, 31, 1202-10. https://doi.org/10.1093/carcin/bgq078
  94. Wang Y, Yamaguchi H, Hsu J. et al (2010). Nuclear trafficking of the epidermal growth factor receptor family membrane proteins. Oncogene, 29, 3997-4006. https://doi.org/10.1038/onc.2010.157
  95. Weihua Z, Tsan R, Huang WC, et al (2008). Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell, 13, 385-93. https://doi.org/10.1016/j.ccr.2008.03.015
  96. Xia W, Wei Y, Du Y, et al (2009). Nuclear expression of epidermal growth factor receptor is a novel prognosticvalue in patients with ovarian cancer. Mol Carcinog, 48, 610-7. https://doi.org/10.1002/mc.20504
  97. Yamamoto C, Basaki Y, Kawahara A, et al (2010). Loss of PTEN expression by blocking nuclear translocation of EGR1 in gefitinib-resistant lung cancer cells harboring epidermal growth factor receptor-activating mutations. Cancer Res, 70, 8715-25. https://doi.org/10.1158/0008-5472.CAN-10-0043
  98. Yamazaki T, Zaal K, Hailey D, et al (2002). Role of Grb2 in EGF-stimulated EGFR internalization. J Cell Sci, 115, 1791-802.
  99. Yang W, Xia Y, Ji H, et al (2011). Nuclear PKM2 regulates beta-catenin transactivation upon EGFR activation. Nature, 480, 118-22.
  100. Yu J, Zhang SS, Saito K, et al (2009). PTEN regulation by Akt-EGR1-ARF-PTEN axis. EMBO J, 28, 21-33. https://doi.org/10.1038/emboj.2008.238
  101. Yun CH, Boggon TJ, Li Y, et al (2007). Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell, 11, 217-27. https://doi.org/10.1016/j.ccr.2006.12.017
  102. Zander T, Scheffler M, Nogova L, et al (2011). Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F] fluorodeoxyglucose and [(18)F]fluorothymidinepositron emission tomography. J Clin Oncol, 29, 1701-8. https://doi.org/10.1200/JCO.2010.32.4939
  103. Zhang L, Ge W, Hu K, et al (2012). Endostar down-regulates HIF-1 and VEGF expression and enhances the radioresponse to human lung adenocarcinoma cancer cells. Mol Biol Rep, 39, 89-95. https://doi.org/10.1007/s11033-011-0713-6
  104. Zhong H, Chiles K, Feldser D, et al (2000). Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res, 60, 1541-5.
  105. Zhong L, Roybal J, Chaerkady R, et al (2008). Identification of secreted proteins that mediate cell-cell interactions in an in vitro model of the lung cancer microenvironment. Cancer Res, 68, 7237-45. https://doi.org/10.1158/0008-5472.CAN-08-1529
  106. Zhou C, Wu YL, Chen G, et al (2011). Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): amulticentre, open-label, randomised, phase 3 study. Lancet Oncol, 12, 735-42. https://doi.org/10.1016/S1470-2045(11)70184-X

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