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Epigenetics in lung cancer diagnosis and therapy

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Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. The initiation and progression of lung cancer is the result of the interaction between permanent genetic and dynamic epigenetic alterations. DNA methylation is the best studied epigenetic mark in human cancers. Altered DNA methylation in cancer was identified in 1983. Within 30 years of this discovery, DNA methylation inhibitors are used clinically to treat a variety of cancers, highlighting the importance of the epigenetic basis of cancer. In addition, histone modifications, nucleosome remodeling, and micro RNA (miRNA)-mediated gene regulation are also fundamental to tumor genesis. Distinct chromatin alterations occur in all stages of lung cancer, including initiation, growth, and metastasis. Therefore, stage-specific epigenetic changes can be used as powerful and reliable tools for early diagnosis of lung cancer and to monitor patient prognosis. Moreover, since epigenetic changes are dynamic and reversible, chromatin modifiers are promising targets for the development of more effective therapeutic strategies against cancer. This review summarizes the chromatin alterations in lung cancer, focusing on the diagnostic and therapeutic approaches targeting epigenetic modifications that could help to reduce the high case-fatality rate of this dreadful disease.

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References

  1. Balgkouranidou, I., Liloglou, T., & Lianidou, E. S. (2013). Lung cancer epigenetics: emerging biomarkers. Biomarkers in Medicine, 7(1), 49–58.

    Article  CAS  PubMed  Google Scholar 

  2. Molina, J. R., et al. (2008). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proceedings, 83(5), 584–594.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Herbst, R. S., Heymach, J. V., & Lippman, S. M. (2008). Lung cancer. New England Journal of Medicine, 359(13), 1367–1380.

    Article  CAS  PubMed  Google Scholar 

  4. Hoffman, P. C., Mauer, A. M., & Vokes, E. E. (2000). Lung cancer. Lancet, 355(9202), 479–485.

    Article  CAS  PubMed  Google Scholar 

  5. Nemeth, A., & Langst, G. (2004). Chromatin higher order structure: opening up chromatin for transcription. Briefings in Functional Genomics & Proteomics, 2(4), 334–343.

    Article  CAS  Google Scholar 

  6. Zhang, Y. (2011). Recent progress in the epigenetics and chromatin field. Cell Research, 21(3), 373–374.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Brzezianska, E., Dutkowska, A., & Antczak, A. (2013). The significance of epigenetic alterations in lung carcinogenesis. Molecular Biology Reports, 40(1), 309–325.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Ozturk, N., Singh, I., Mehta, A., Braun, T., & Barreto, G. HMGA proteins as modulators of chromatin structure during transcriptional activation. Frontiers in Cell and Developmental Biology.

  9. Esteller, M. (2008). Epigenetics in cancer. New England Journal of Medicine, 358(11), 1148–1159.

    Article  CAS  PubMed  Google Scholar 

  10. Deaton, A. M., & Bird, A. (2011). CpG islands and the regulation of transcription. Genes and Development, 25(10), 1010–1022.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Cedar, H., & Bergman, Y. (2009). Linking DNA methylation and histone modification: patterns and paradigms. Nature Reviews Genetics, 10(5), 295–304.

    Article  CAS  PubMed  Google Scholar 

  12. Wang, Y., et al. (2004). Beyond the double helix: writing and reading the histone code. Novartis Foundation Symposium, 259, 3–17. discussion 17–21, 163–9.

    Article  CAS  PubMed  Google Scholar 

  13. Knudson, A. G., Jr. (1971). Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences of the United States of America, 68(4), 820–823.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Kim, H., et al. (2006). Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Cancer, 107(5), 1042–1049.

    Article  CAS  PubMed  Google Scholar 

  15. Lin, R. K., et al. (2007). Alteration of DNA methyltransferases contributes to 5′CpG methylation and poor prognosis in lung cancer. Lung Cancer, 55(2), 205–213.

    Article  PubMed  Google Scholar 

  16. Feinberg, A. P., & Vogelstein, B. (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature, 301(5895), 89–92.

    Article  CAS  PubMed  Google Scholar 

  17. Weber, M., et al. (2005). Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nature Genetics, 37(8), 853–862.

    Article  CAS  PubMed  Google Scholar 

  18. Rauch, T. A., et al. (2008). High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 105(1), 252–257.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Lander, E. S., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6822), 860–921.

    Article  CAS  PubMed  Google Scholar 

  20. Gaudet, F., et al. (2003). Induction of tumors in mice by genomic hypomethylation. Science, 300(5618), 489–492.

    Article  CAS  PubMed  Google Scholar 

  21. Gupta, P. K., et al. (1997). High frequency in vivo loss of heterozygosity is primarily a consequence of mitotic recombination. Cancer Research, 57(6), 1188–1193.

    CAS  PubMed  Google Scholar 

  22. Holt, D., et al. (1999). Interindividual variation in mitotic recombination. American Journal of Human Genetics, 65(5), 1423–1427.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Maloisel, L., & Rossignol, J. L. (1998). Suppression of crossing-over by DNA methylation in Ascobolus. Genes and Development, 12(9), 1381–1389.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Kim, M., et al. (2004). Dnmt1 deficiency leads to enhanced microsatellite instability in mouse embryonic stem cells. Nucleic Acids Research, 32(19), 5742–5749.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Beck, C. R., et al. (2011). LINE-1 elements in structural variation and disease. Annual Review of Genomics and Human Genetics, 12, 187–215.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Sargurupremraj, M., & Wjst, M. (2013). Transposable elements and their potential role in complex lung disorder. Respiratory Research, 14, 99.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Iskow, R. C., et al. (2010). Natural mutagenesis of human genomes by endogenous retrotransposons. Cell, 141(7), 1253–1261.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Dupuy, A. J., et al. (2005). Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature, 436(7048), 221–226.

    Article  CAS  PubMed  Google Scholar 

  29. Collier, L. S., et al. (2005). Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature, 436(7048), 272–276.

    Article  CAS  PubMed  Google Scholar 

  30. Xing, J., et al. (2009). Mobile elements create structural variation: analysis of a complete human genome. Genome Research, 19(9), 1516–1526.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Lujambio, A., et al. (2010). CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene, 29(48), 6390–6401.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Lin, S. H., et al. (2014). Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial-mesenchymal transition. BMC Genomics, 15, 1079.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Thiery, J. P., et al. (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139(5), 871–890.

    Article  CAS  PubMed  Google Scholar 

  34. Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. Journal of Clinical Investigation, 119(6), 1420–1428.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Le Bras, G. F., Taubenslag, K. J., & Andl, C. D. (2012). The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression. Cell Adhesion & Migration, 6(4), 365–373.

    Article  Google Scholar 

  36. Richardson, F., et al. (2012). The evaluation of E-Cadherin and vimentin as biomarkers of clinical outcomes among patients with non-small cell lung cancer treated with erlotinib as second- or third-line therapy. Anticancer Research, 32(2), 537–552.

    CAS  PubMed  Google Scholar 

  37. Xiao, D., & He, J. (2010). Epithelial mesenchymal transition and lung cancer. Journal of Thoracic Disease, 2(3), 154–159.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Singh, A., & Settleman, J. (2010). EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 29(34), 4741–4751.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Fu, J., et al. (2011). The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. Cell Research, 21(2), 275–289.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Yang, J., et al. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117(7), 927–939.

    Article  CAS  PubMed  Google Scholar 

  41. Tran, P. T., et al. (2012). Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. PLoS Genetics, 8(5), e1002650.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. De Craene, B., & Berx, G. (2013). Regulatory networks defining EMT during cancer initiation and progression. Nature Reviews Cancer, 13(2), 97–110.

    Article  PubMed  CAS  Google Scholar 

  43. Van’t Westeinde, S. C., & van Klaveren, R. J. (2011). Screening and early detection of lung cancer. Cancer Journal, 17(1), 3–10.

    Article  Google Scholar 

  44. Mulshine, J. L. (2003). Screening for lung cancer: in pursuit of pre-metastatic disease. Nature Reviews Cancer, 3(1), 65–73.

    Article  CAS  PubMed  Google Scholar 

  45. Marshall, H. M., et al. (2013). Screening for lung cancer with low-dose computed tomography: a review of current status. Journal of Thoracic Disease, 5(Suppl 5), S524–S539.

    PubMed Central  PubMed  Google Scholar 

  46. Siegel, R., Naishadham, D., & Jemal, A. (2013). Cancer statistics, 2013. CA: A Cancer Journal for Clinicians, 63(1), 11–30.

    Google Scholar 

  47. Ahrendt, S. A., et al. (1999). Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. Journal of the National Cancer Institute, 91(4), 332–339.

    Article  CAS  PubMed  Google Scholar 

  48. Selamat, S. A., et al. (2011). DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in situ, and lung adenocarcinoma. PLoS One, 6(6), e21443.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Yanagawa, N., et al. (2003). Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers. Cancer Science, 94(7), 589–592.

    Article  CAS  PubMed  Google Scholar 

  50. Pulling, L. C., et al. (2003). Promoter hypermethylation of the O6-methylguanine-DNA methyltransferase gene: more common in lung adenocarcinomas from never-smokers than smokers and associated with tumor progression. Cancer Research, 63(16), 4842–4848.

    CAS  PubMed  Google Scholar 

  51. Kim, J. S., et al. (2005). Aberrant methylation of H-cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma. Cancer, 104(9), 1825–1833.

    Article  CAS  PubMed  Google Scholar 

  52. Lin, Q., et al. (2009). RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China. Journal of Cancer Research and Clinical Oncology, 135(12), 1675–1684.

    Article  CAS  PubMed  Google Scholar 

  53. Kneip, C., et al. (2011). SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma. Journal of Thoracic Oncology, 6(10), 1632–1638.

    Article  PubMed  Google Scholar 

  54. Tsou, J. A., et al. (2007). Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Molecular Cancer, 6, 70.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  55. Niklinska, W., et al. (2009). Prognostic significance of DAPK and RASSF1A promoter hypermethylation in non-small cell lung cancer (NSCLC). Folia Histochemica et Cytobiologica, 47(2), 275–280.

    Article  CAS  PubMed  Google Scholar 

  56. Risse, E. K., et al. (1985). Sputum cytology by the Saccomanno method in diagnosing lung malignancy. Diagnostic Cytopathology, 1(4), 286–291.

    Article  CAS  PubMed  Google Scholar 

  57. Hubers, A. J., et al. (2014). Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis. Journal of Clinical Pathology, 67(8), 707–711.

    Article  PubMed  Google Scholar 

  58. Leng, S., et al. (2012). Defining a gene promoter methylation signature in sputum for lung cancer risk assessment. Clinical Cancer Research, 18(12), 3387–3395.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Wang, Y. C., et al. (2003). Inactivation of hMLH1 and hMSH2 by promoter methylation in primary non-small cell lung tumors and matched sputum samples. Journal of Clinical Investigation, 111(6), 887–895.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Liu, Y., et al. (2003). Hypermethylation of p16INK4a in Chinese lung cancer patients: biological and clinical implications. Carcinogenesis, 24(12), 1897–1901.

    Article  CAS  PubMed  Google Scholar 

  61. Destro, A., et al. (2004). K-ras and p16(INK4A)alterations in sputum of NSCLC patients and in heavy asymptomatic chronic smokers. Lung Cancer, 44(1), 23–32.

    Article  CAS  PubMed  Google Scholar 

  62. Belinsky, S. A., et al. (2007). Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum. British Journal of Cancer, 96(8), 1278–1283.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Cirincione, R., et al. (2006). Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: a nested case–control study. International Journal of Cancer, 118(5), 1248–1253.

    Article  CAS  Google Scholar 

  64. Ammanagi, A. S., et al. (2012). Sputum cytology in suspected cases of carcinoma of lung (Sputum cytology a poor man’s bronchoscopy!). Lung India, 29(1), 19–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Hsu, H. S., et al. (2007). Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma. Cancer, 110(9), 2019–2026.

    Article  CAS  PubMed  Google Scholar 

  66. Suga, Y., et al. (2008). Quantitative p16 and ESR1 methylation in the peripheral blood of patients with non-small cell lung cancer. Oncology Reports, 20(5), 1137–1142.

    CAS  PubMed  Google Scholar 

  67. Bearzatto, A., et al. (2002). p16(INK4A) Hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer. Clinical Cancer Research, 8(12), 3782–3787.

    CAS  PubMed  Google Scholar 

  68. Russo, A. L., et al. (2005). Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clinical Cancer Research, 11(7), 2466–2470.

    Article  CAS  PubMed  Google Scholar 

  69. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674.

    Article  CAS  PubMed  Google Scholar 

  70. Boedeker, E., Friedel, G., & Walles, T. (2012). Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening. Interactive Cardiovascular and Thoracic Surgery, 14(5), 511–515.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Rattray, N. J., et al. (2014). Taking your breath away: metabolomics breathes life in to personalized medicine. Trends in Biotechnology, 32(10), 538–548.

    Article  CAS  PubMed  Google Scholar 

  72. Dent, A. G., Sutedja, T. G., & Zimmerman, P. V. (2013). Exhaled breath analysis for lung cancer. Journal of Thoracic Disease, 5(Suppl 5), S540–S550.

    PubMed Central  PubMed  Google Scholar 

  73. Xiao, P., et al. (2014). Methylation of P16 in exhaled breath condensate for diagnosis of non-small cell lung cancer. Lung Cancer, 83(1), 56–60.

    Article  PubMed  Google Scholar 

  74. Han, W., et al. (2009). Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients. Respiratory Research, 10, 86.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Filipowicz, W., Bhattacharyya, S. N., & Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Reviews Genetics, 9(2), 102–114.

    Article  CAS  PubMed  Google Scholar 

  76. Ebert, M. S., & Sharp, P. A. (2012). Roles for microRNAs in conferring robustness to biological processes. Cell, 149(3), 515–524.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Calin, G. A., et al. (2004). MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proceedings of the National Academy of Sciences of the United States of America, 101(32), 11755–11760.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Lu, J., et al. (2005). MicroRNA expression profiles classify human cancers. Nature, 435(7043), 834–838.

    Article  CAS  PubMed  Google Scholar 

  79. Trang, P., et al. (2010). Regression of murine lung tumors by the let-7 microRNA. Oncogene, 29(11), 1580–1587.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Johnson, S. M., et al. (2005). RAS is regulated by the let-7 microRNA family. Cell, 120(5), 635–647.

    Article  CAS  PubMed  Google Scholar 

  81. Takamizawa, J., et al. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Research, 64(11), 3753–3756.

    Article  CAS  PubMed  Google Scholar 

  82. Hayashita, Y., et al. (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Research, 65(21), 9628–9632.

    Article  CAS  PubMed  Google Scholar 

  83. Donnem, T., et al. (2012). MicroRNA signatures in tumor tissue related to angiogenesis in non-small cell lung cancer. PLoS One, 7(1), e29671.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Boeri, M., et al. (2011). MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3713–3718.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Pritchard, C. C., Cheng, H. H., & Tewari, M. (2012). MicroRNA profiling: approaches and considerations. Nature Reviews Genetics, 13(5), 358–369.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Nair, V. S., Maeda, L. S., & Ioannidis, J. P. (2012). Clinical outcome prediction by microRNAs in human cancer: a systematic review. Journal of the National Cancer Institute, 104(7), 528–540.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Cagle, P. T., & Chirieac, L. R. (2012). Advances in treatment of lung cancer with targeted therapy. Archives of Pathology and Laboratory Medicine, 136(5), 504–509.

    Article  CAS  PubMed  Google Scholar 

  88. (2011) In The diagnosis and treatment of lung cancer (Update). Cardiff (UK).

  89. Schuchert, M. J., et al. (2010). Sublobar resection for early-stage lung cancer. Seminars in Thoracic and Cardiovascular Surgery, 22(1), 22–31.

    Article  PubMed  Google Scholar 

  90. Sonke, J. J., & Belderbos, J. (2010). Adaptive radiotherapy for lung cancer. Seminars in Radiation Oncology, 20(2), 94–106.

    Article  PubMed  Google Scholar 

  91. Pfister, D. G., et al. (2004). American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. Journal of Clinical Oncology, 22(2), 330–353.

    Article  PubMed  Google Scholar 

  92. Simone, C. B., 2nd, et al. (2013). Stereotactic body radiation therapy for lung cancer. Chest, 143(6), 1784–1790.

    Article  CAS  PubMed  Google Scholar 

  93. Timmerman, R., et al. (2010). Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA, 303(11), 1070–1076.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Ma, P.C. (2012). Personalized targeted therapy in advanced non-small cell lung cancer. Cleveland Clinic Journal of Medicine, (79 Electronic Suppl 1), eS56–60.

  95. Sandler, A., et al. (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New England Journal of Medicine, 355(24), 2542–2550.

    Article  CAS  PubMed  Google Scholar 

  96. Davies, M. (2014). New modalities of cancer treatment for NSCLC: focus on immunotherapy. Cancer Management and Research, 6, 63–75.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  97. Hatzimichael, E., & Crook, T. (2013). Cancer epigenetics: new therapies and new challenges. Journal of Drug Delivery, 2013, 529312.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  98. Jones, P. A., & Baylin, S. B. (2007). The epigenomics of cancer. Cell, 128(4), 683–692.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Chuang, J. C., & Jones, P. A. (2007). Epigenetics and microRNAs. Pediatric Research, 61(5 Pt 2), 24R–29R.

    Article  CAS  PubMed  Google Scholar 

  100. Dawson, M. A., & Kouzarides, T. (2012). Cancer epigenetics: from mechanism to therapy. Cell, 150(1), 12–27.

    Article  CAS  PubMed  Google Scholar 

  101. Keohane, C., Mesa, R., & Harrison, C. (2013). The role of JAK1/2 inhibitors in the treatment of chronic myeloproliferative neoplasms. American Society of Clinical Oncology Educational Book, 301–305.

  102. Liu, S. V., et al. (2013). Epigenetic therapy in lung cancer. Frontiers in Oncology, 3, 135.

    Article  PubMed Central  PubMed  Google Scholar 

  103. Lyko, F., & Brown, R. (2005). DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. Journal of the National Cancer Institute, 97(20), 1498–1506.

    Article  CAS  PubMed  Google Scholar 

  104. Tang, M., et al. (2009). Potential of DNMT and its epigenetic regulation for lung cancer therapy. Current Genomics, 10(5), 336–352.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  105. Christman, J. K. (2002). 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene, 21(35), 5483–5495.

    Article  CAS  PubMed  Google Scholar 

  106. Komashko, V. M., & Farnham, P. J. (2010). 5-azacytidine treatment reorganizes genomic histone modification patterns. Epigenetics, 5(3), 229–240.

    Article  CAS  PubMed  Google Scholar 

  107. Kim, H. J., & Bae, S. C. (2011). Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. American Journal of Translational Research, 3(2), 166–179.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Brazelle, W., et al. (2010). Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. PLoS One, 5(12), e14335.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Tang, Y. A., et al. (2010). A novel histone deacetylase inhibitor exhibits antitumor activity via apoptosis induction, F-actin disruption and gene acetylation in lung cancer. PLoS One, 5(9), e12417.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  110. Perrino, E., et al. (2008). New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity. Bioorganic and Medicinal Chemistry Letters, 18(6), 1893–1897.

    Article  CAS  PubMed  Google Scholar 

  111. Tesei, A., et al. (2012). Organosulfur derivatives of the HDAC inhibitor valproic acid sensitize human lung cancer cell lines to apoptosis and to cisplatin cytotoxicity. Journal of Cellular Physiology, 227(10), 3389–3396.

    Article  CAS  PubMed  Google Scholar 

  112. Zhang, W., et al. (2009). Histone deacetylase inhibitor romidepsin enhances anti-tumor effect of erlotinib in non-small cell lung cancer (NSCLC) cell lines. Journal of Thoracic Oncology, 4(2), 161–166.

    Article  PubMed Central  PubMed  Google Scholar 

  113. Karthik, S., et al. (2014). Romidepsin induces cell cycle arrest, apoptosis, histone hyperacetylation and reduces matrix metalloproteinases 2 and 9 expression in bortezomib sensitized non-small cell lung cancer cells. Biomedicine and Pharmacotherapy, 68(3), 327–334.

    Article  CAS  PubMed  Google Scholar 

  114. Papeleu, P., et al. (2003). Trichostatin A induces differential cell cycle arrests but does not induce apoptosis in primary cultures of mitogen-stimulated rat hepatocytes. Journal of Hepatology, 39(3), 374–382.

    Article  CAS  PubMed  Google Scholar 

  115. Mukhopadhyay, N. K., et al. (2006). Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer. Annals of Thoracic Surgery, 81(3), 1034–1042.

    Article  PubMed  Google Scholar 

  116. Platta, C. S., et al. (2007). The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. Journal of Surgical Research, 142(2), 219–226.

    Article  CAS  PubMed  Google Scholar 

  117. Juergens, R.A., & Rudin, C.M. (2013). Aberrant epigenetic regulation: a central contributor to lung carcinogenesis and a new therapeutic target. American Society of Clinical Oncology Educational Book.

  118. Petta, V., et al. (2013). Histones and lung cancer: are the histone deacetylases a promising therapeutic target? Cancer Chemotherapy and Pharmacology, 72(5), 935–952.

    Article  CAS  PubMed  Google Scholar 

  119. Li, C. T., et al. (2011). Vorinostat, SAHA, represses telomerase activity via epigenetic regulation of telomerase reverse transcriptase in non-small cell lung cancer cells. Journal of Cellular Biochemistry, 112(10), 3044–3053.

    Article  CAS  PubMed  Google Scholar 

  120. Forde, P. M., Brahmer, J. R., & Kelly, R. J. (2014). New strategies in lung cancer: epigenetic therapy for non-small cell lung cancer. Clinical Cancer Research, 20(9), 2244–2248.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  121. Belinsky, S. A., et al. (2011). Combination therapy with Vidaza and entinostat suppresses tumor growth and reprograms the epigenome in an orthotopic lung cancer model. Cancer Research, 71(2), 454–462.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  122. Noro, R., et al. (2007). PTEN inactivation in lung cancer cells and the effect of its recovery on treatment with epidermal growth factor receptor tyrosine kinase inhibitors. International Journal of Oncology, 31(5), 1157–1163.

    CAS  PubMed  Google Scholar 

  123. Peipp, M., et al. (2002). A recombinant CD7-specific single-chain immunotoxin is a potent inducer of apoptosis in acute leukemic T cells. Cancer Research, 62(10), 2848–2855.

    CAS  PubMed  Google Scholar 

  124. Deng, X. K., Nesbit, L. A., & Morrow, K. J., Jr. (2003). Recombinant single-chain variable fragment antibodies directed against Clostridium difficile toxin B produced by use of an optimized phage display system. Clinical and Diagnostic Laboratory Immunology, 10(4), 587–595.

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Frenzel, A., Hust, M., & Schirrmann, T. (2013). Expression of recombinant antibodies. Frontiers in Immunology, 4, 217.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  126. Wang, R., et al. (2013). Engineering production of functional scFv antibody in E. coli by co-expressing the molecule chaperone Skp. Frontiers in Cellular and Infection Microbiology, 3, 72.

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Kumar, P., et al. (2008). T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell, 134(4), 577–586.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Xu, X., et al. (2012). Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma. Proceedings of the National Academy of Sciences of the United States of America, 109(13), 4910–4915.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  129. Oh, Y. K., & Park, T. G. (2009). siRNA delivery systems for cancer treatment. Advanced Drug Delivery Reviews, 61(10), 850–862.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Indrabahadur Singh and Julio Cordero for helpful discussions. This work was done according to the program for competitive growth of the Kazan Federal University and the Russian Government. Addi J. Romero-Olmedo received a fellowship from CONACyT - COCyT (CVU 510283). Guillermo Barreto is funded by the „LOEWE-Initiative der Landesförderung“ (III L4–18/15.004 2009) and the DFG grant BA 4036/1-1.

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Authors and Affiliations

  1. LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany

    Aditi Mehta, Stephanie Dobersch, Addi J. Romero-Olmedo & Guillermo Barreto

  2. Facultad de Ciencias Químicas, Universidad Autonoma “Benito Juarez” de Oaxaca, Oaxaca, Mexico

    Addi J. Romero-Olmedo

  3. Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008, Kazan, Russian Federation

    Guillermo Barreto

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  1. Aditi Mehta
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  2. Stephanie Dobersch
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  3. Addi J. Romero-Olmedo
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  4. Guillermo Barreto
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Correspondence to Guillermo Barreto.

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Affiliations in Germany are members of the Universities of Giessen and Marburg Lung Center (UGMLC) and the German Center of Lung Research (DZL).

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Mehta, A., Dobersch, S., Romero-Olmedo, A.J. et al. Epigenetics in lung cancer diagnosis and therapy. Cancer Metastasis Rev 34, 229–241 (2015). https://doi.org/10.1007/s10555-015-9563-3

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