Epigenetic therapy in lung cancer

Frontiers in Oncology

Volumn 3 MAY, Issue , 2013, Pages

  Liu, Stephen V ^a   Fabbri, Muller ^a   Gitlitz, Barbara J ^a   Laird Offringa, Ite A ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

DNA methylation; Epigenetics; Histone deacetylase inhibitors; Hypomethylating agent; Lung cancer; MicroRNAs

Indexed keywords

4 PHENYLBUTYRIC ACID; 5 AZA 2' DEOXYCYTIDINE; 6 (1, 3 DIOXO 1H, 3H BENZO [DE] ISOQUINOLIN 2 YL) N HYDROXYHEXANAMIDE; 6 (1,3 DIOXO 1H,3H BENZO[DE]ISOQUINOLIN 2 YL) N HYDROXYHEXANAMIDE; APICIDIN; BORTEZOMIB; CARBOPLATIN; CISPLATIN; DOXORUBICIN; ENTINOSTAT; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEMCITABINE; HONOKIOL; HYDRALAZINE; MICRORNA; MICRORNA 9; NIVOLUMAB; PACLITAXEL; PANOBINOSTAT; PLATINUM; ROMIDEPSIN; STAT3 PROTEIN; TAXANE DERIVATIVE; TRICHOSTATIN A; UNCLASSIFIED DRUG; VALPROATE MAGNESIUM; VALPROIC ACID; VORINOSTAT;

ADJUVANT THERAPY; CONTINUOUS INFUSION; DEACETYLATION; DEREGULATION; DNA METHYLATION; DNA TRANSCRIPTION; EPIGENETICS; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE MUTATION; GENE SILENCING; HISTONE ACETYLATION; HISTONE MODIFICATION; HUMAN; LUNG CANCER; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; MULTIPLE CYCLE TREATMENT; NEUROTOXICITY; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW; TUMOR GROWTH;

EID: 84886716989     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00135     Document Type: Review

References (92)

1. Ambros, V. (2003). MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113, 673-676. doi:10.1016/S0092-8674(03)00428-8
2. Anglim, P. P., Galler, J. S., Koss, M. N., Hagen, J. A., Turla, S., Campan, M., et al. (2008). Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer. Mol. Cancer 7, 62. doi:10.1186/1476-4598-7-62
3. Baer, C., Claus, R., and Plass, C. (2013). Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 73, 473-477. doi:10.1158/0008-5472.CAN-12-3731
4. Barneda-Zahonero, B., and Parra, M. (2012). Histone deacetylases and cancer. Mol. Oncol. 6, 579-589. doi:10.1016/j.molonc.2012.07.003
5. Baylin, S. B., and Jones, P. A. (2011). A decade of exploring the cancer epigenome-biological and translational implications. Nat. Rev. Cancer 11, 726-734. doi:10.1038/nrc3130
6. Belinsky, S. A., Grimes, M. J., Picchi, M. A., Mitchell, H. D., Stidley, C. A., Tesfaigzi, Y., et al. (2011). Combination therapy with Vidaza and entinostat suppresses tumor growth and reprograms the epigenome in an orthotopic lung cancer model. Cancer Res. 71, 454-462. doi:10.1158/0008-5472.CAN-10-3184
7. Belinsky, S. A., Liechty, K. C., Gentry, F. D., Wolf, H. J., Rogers, J., Vu, K., et al. (2006). Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res. 66, 3338-3344. doi:10.1158/0008-5472.CAN-05-3408
8. Belinsky, S. A., Nikula, K. J., Palmisano, W. A., Michels, R., Saccomanno, G., Gabrielson, E., et al. (1998). Aberrant methylation of p16(INJK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc. Natl. Acad. Sci. U.S.A. 95, 11891-11896. doi:10.1073/pnas.95.20.11891
9. Belinsky, S. A., Palmisano, W. A., Gilliland, F. D., Crooks, L. A., Divine, K. K., Winters, S. A., et al. (2002). Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res. 62, 2370-2377.
10. Brazelle, W., Kreahling, J. M., Gemmer, J., Ma, Y., Cress, W. D., Haura, E., et al. (2010). Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. PLoS ONE 14:e14335. doi:10.1371/journal.pone.0014335
11. Brock, M. V., Hooker, C. M., Ota-Machida, E., Han, Y., Guo, M., Ames, S., et al. (2008). DNA methylation markers and early recurrence in stage I lung cancer. N. Engl. J. Med. 358, 1118-1128. doi:10.1056/NEJMoa0706550
12. Brueckner, B., Stresemann, C., Kuner, R., Mund, C., Musch, T., Meister, M., et al. (2007). The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 67, 1419-1423. doi:10.1158/0008-5472.CAN-06-4074
13. Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G., and Baylin, S. B. (1999). Synergy of demethylation and histone deacetylation in the re-expression of genes silenced in cancer. Nat. Genet. 21, 103-107. doi:10.1038/5047
14. Candelaria, M., Gallardo-Rincon, D., Arce, C., Cetina, L., Aguilar-Ponce, J. L., Arrieta, O., et al. (2007). A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann. Oncol. 18, 1529-1538. doi:10.1093/annonc/mdm204
15. Cantor, J. P., Iliopoulos, D., Rao, A. S., Druck, T., Semba, S., Han, S. Y., et al. (2006). Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity. Int. J. Cancer 120, 24-31. doi:10.1002/ijc.22073
16. Carvalho, R. H., Haberle, V., Hou, J., van Gent, T., Thongjuea, S., van Ijcken, W., et al. (2012). Genome-wide DNA methylation profiling of non-small cell lung carcinomas. Epigenetics Chromatin 5, 9. doi:10.1186/1756-8935-5-9
17. Castoldi, M., Schmidt, S., Benes, V., Noerholm, M., Kulozik, A. E., Hentze, M. W., et al. (2006). A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA 12, 913-920. doi:10.1261/rna.2332406
18. Chen, J. F., Mandel, E. M., Thomson, J. M., Wu, Q., Callis, T. E., Hammond, S. M., et al. (2006). The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat. Genet. 38, 228-233. doi:10.1038/ng1725
19. Chen, P. S., Su, J. L., and Hung, M. C. (2012). Dysregulation of microRNAs in cancer. J. Biomed. Sci. 19, 90. doi:10.1186/1423-0127-19-90
20. Chen, S. H., and Zhaori, G. (2010). Potential clinical applications of siRNA technique: benefits and limitations. Eur. J. Clin. Invest. 41, 221-232. doi:10.1111/j.1365-2362.2010.02400.x
21. Chu, B. F., Karpenko, M. J., Liu, Z., Aimiuwu, J., Villalona-Calero, M. A., Chan, K. K., and Etalname, A. (2013). Phase I study of 5-aza-2'-deoxycytidine in combination with valproic acid in non-small-cell lung cancer. Cancer Chemother. Pharmacol. 71, 115-121. doi:10.1007/s00280-012-1986-8
22. Clayton, A., Hazzalin, C., and Mahadevan, L. (2006). Enhanced histone acetylation and transcription: a dynamic perspective. Mol. Cell 23, 289-296. doi:10.1016/j.molcel.2006.06.017
23. Coiffier, B., Pro, B., Prince, H. M., Foss, F., Sokol, L., Greenwood, M., et al. (2012). Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J. Clin. Oncol. 30, 631-636. doi:10.1200/JCO.2011.37.4223
24. Croce, C. M. (2011). miRNAs in the spotlight: understanding cancer gene dependency. Nat. Med. 17, 935-936. doi:10.1038/nm0811-935
25. Croce, C. M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet. 10, 704-714. doi:10.1038/nrg2634
26. Daskalakis, M., Nguyen, T. T., Nguyen, C., Guldberg, P., Köhler, G., Wijermans, P., and Etalname, A. (2002). Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment. Blood 100, 2957-2964. doi:10.1182/blood.V100.8.2957
27. Dokmanovic, M., Clarke, C., and Marks, P. A. (2007). Histone deacetylase inhibitors: overview and perspectives. Mol. Cancer Res. 5, 981-989. doi:10.1158/1541-7786.MCR-07-0324
28. Fabbri, M., and Calin, G. A. (2010). Epigenetics and miRNAs in human cancer. Adv. Genet. 70, 87-99. doi:10.1016/B978-0-12-380866-0.60004-6
29. Fabbri, M., Calore, F., Paone, A., Galli, R., and Calin, G. A. (2013). Epigenetic regulation of miRNAs in cancer. Adv. Exp. Med. Biol. 754, 137-148. doi:10.1007/978-1-4419-9967-2_6
30. Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., et al. (2007). MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl. Acad. Sci. U.S.A. 104, 15805-15810. doi:10.1073/pnas.0707628104
31. Garzon, R., Liu, S., Fabbri, M., Liu, Z., Heaphy, C. E., Callegari, E., et al. (2009). MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113, 6411-6418. doi:10.1182/blood-2008-07-170589
32. He, X. W., Yu, X., Liu, T., Yu, S. Y., and Chen, D. J. (2008). Vector-based RNA interference against vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of colorectal cancer in vivo in mice. Chin. Med. J. 121, 439-444.
33. Heller, G., Babinsky, V. N., Ziegler, B., Weinzierl, M., Noll, C., Altenberger, C., et al. (2013). Genome-wide CpG island methylation analyses in non-small cell lung cancer patients. Carcinogenesis 34, 513-521. doi:10.1093/carcin/bgs363
34. Heller, G., Weinzierl, M., Noll, C., Babinsky, V., Ziegler, B., Altenberger, C., et al. (2012). Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets for DNA methylation in non-small cell lung cancers. Clin. Cancer Res. 18, 1619-1629. doi:10.1158/1078-0432.CCR-11-2450
35. Ibanez de Caceres, I., Cortes-Sempere, M., Moratilla, C., Machado-Pinilla, R., Rodriguez-Fanjul, V., Manguan-Garcia, C., et al. (2010). IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer. Oncogene 29, 1681-1690. doi:10.1038/onc.2009.454
36. Incoronato, M., Garofalo, M., Urso, L., Romano, G., Quintavalle, C., Zanca, C., et al. (2010). miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. Cancer Res. 70, 3638-3646. doi:10.1158/0008-5472.CAN-09-3341
37. Incoronato, M., Urso, L., Portela, A., Laukkanen, M. O., Soini, Y., Quintavalle, C., et al. (2011). Epigenetic regulation of miR-212 expression in lung cancer. PLoS ONE 6:e27722. doi:10.1371/journal.pone.0027722
38. Jones, D. R., Moskaluk, C. A., Gillenwater, H. H., Petroni, G. R., Burks, S. G., Philips, J., et al. (2012). Phase I trial of induction histone deacetylase and proteasome inhibition followed by surgery in non-small cell lung cancer. J. Thorac. Oncol. 7, 1683-1690. doi:10.1097/JTO.0b013e318267928d
39. Jones, P. A. (2012). Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484-492. doi:10.1038/nrg3230
40. Jones, P. A., Taylor, S. M., and Wilson, V. L. (1983). Inhibition of DNA methylation by 5-azacytidine. Recent Results Cancer Res. 84, 202-211.
41. Juergens, R. A., Wrangle, J., Vendetti, F. P., Murphy, S. C., Zhao, M., Coleman, B., et al. (2011). Combination epigenetic therapy has efficacy in patients with refractory advanced non small cell lung cancer. Cancer Discov. 1, 598-607. doi:10.1158/2159-8290.CD-11-0214
42. Kalari, S., Jung, M., Kernstine, K. H., Takahashi, T., and Pfeifer, G. P. (2012). The DNA methylation landscape of small cell lung cancer suggests a differentiation defect of neuroendocrine cells. Oncogene doi:10.1038/onc.2012.362. [Epub ahead of print].
43. Kaminskyy, V. O., Surova, O. V., Vaculova, A., and Zhivotovsky, B. (2011). Combined inhibition of DNA methyltransferase and histone deacetylase restores caspase-8 expression and sensitizes SCLC cells to TRAIL. Carcinogenesis 32, 1450-1458. doi:10.1093/carcin/bgr135
44. Kanai, Y., and Hirohashi, S. (2007). Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 28, 2434-2442. doi:10.1093/carcin/bgm206
45. Kim, D. H., Nelson, H. H., Wiencke, J. K., Zheng, S., Christiani, D. C., Wain, J. C., et al. (2001). p16INK4a and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer. Cancer Res. 61, 3419-3424.
46. Krutzfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., et al. (2005). Silencing of microRNAs in vivo with 'antagomirs.' Nature 438, 685-689. doi:10.1038/nature04303
47. Kulesza, D. W., Carre, T., Chouaib, S., and Kaminski, B. (2013). Silencing of the transcription factor STAT3 sensitizes lung cancer cells to DNA damaging drugs, but not to TNFa and NK cytotoxicity. Exp. Cell Res. 319, 506-516. doi:10.1016/j.yexcr.2012.11.005
48. Kunze, D., Wuttig, D., Kausch, I., Blietz, C., Blumhoff, L., Burmeister, Y., et al. (2008). Antisense-mediated inhibition of survivin, hTERT and VEGF in bladder cancer cells in vitro and in vivo. Int. J. Oncol. 32, 1049-1056.
49. Kwon, Y. J., Lee, S. J., Koh, J. S., Kim, S. H., Lee, H. W., Kang, M. C., et al. (2012). Genome-wide analysis of DNA methylation and the gene expression change in lung cancer. J. Thorac. Oncol. 7, 20-33. doi:10.1097/JTO.0b013e3182307f62
50. Laird, P. W. (2005). Cancer epigenetics. Hum. Mol. Genet. 14, R65-76. doi:10.1093/hmg/ddi113
51. Lin, J., Gilbert, J., Rudek, M. A., Zwiebel, J. A., Gore, S., Jiemjit, A., et al. (2009). A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin. Cancer Res. 15, 6241-6249. doi:10.1158/1078-0432.CCR-09-0567
52. Lockwood, W. W., Wilson, I. M., Coe, B. P., Chari, R., Pikor, L. A., Thu, K. L., et al. (2012). Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development. PLoS ONE 7:e37775. doi:10.1371/journal.pone.0037775
53. Luchenko, V. L., Salcido, C. D., Zhang, Y., Agama, K., Komlodi-Pasztor, E., Murphy, R. F., et al. (2011). Schedule-dependent synergy of histone deacetylase inhibitors with DNA damaging agents in small cell lung cancer. Cell Cycle 10, 3119-3128. doi:10.4161/cc.10.18.17190
54. Luszczek, W., Cheriyath, V., Mekhail, T. M., and Borden, E. C. (2010). Combinations of DNA methyltransferase and histone deacetylase inhibitors induce DNA damage in small cell lung cancer cells: correlation of resistance with IFN-stimulated gene expression. Mol. Cancer Ther. 9, 2309-2321. doi:10.1158/1535-7163.MCT-10-0309
55. Mayo, M. W., Denlinger, C. E., Broad, R. M., Yeung, F., Reilly, E. T., Shi, Y., et al. (2003). Ineffectiveness of histone deacetylase inhibitors to induce apoptosis involves the transcriptional activation of NF-kB through the Akt pathway. J. Biol. Chem. 278, 18980-18989. doi:10.1074/jbc.M211695200
56. Merlo, A., Herman, J. G., Mao, L., Lee, D. J., Gabrielson, E., Burger, P. C., and Etalname, A. (1995). 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat. Med. 1, 686-692. doi:10.1038/nm0795-686
57. Momparler, R. L., and Ayoub, J. (2001). Potential of 5-aza-2'-deoxycytidine (Decitabine), a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer. Lung Cancer 34, 111-115. doi:10.1016/S0169-5002(01)00397-X
58. Momparler, R. L., Bouffard, D. Y., Momparler, L. F., Dionne, J., Belanger, K., and Ayoub, J. (1997). Pilot phase I-II study on 5-aza-2'-deoxycytidine (Decitabine) in patients with metastatic lung cancer. Anticancer Drugs 8, 358-368. doi:10.1097/00001813-199704000-00008
59. Odate, S., Nakamura, K., Onishi, H., Kojima, M., Uchiyama, A., Nakano, K., et al. (2013). TrkB/BDNF signaling pathway is a potential therapeutic target for pulmonary large cell neuroendocrine carcinoma. Lung Cancer 79, 205-214. doi:10.1016/j.lungcan.2012.12.004
60. Otterson, G. A., Hodgson, L., Pang, H., and Vokes, E. E. (2010). Phase II study of the histone deacetylase inhibitor romidepsin in relapsed small cell lung cancer (Cancer and Leukemia Group B 30304). J. Thorac. Oncol. 5, 1644-1648. doi:10.1097/JTO.0b013e3181ec1713
61. Park, J. Y., Kim, D., Yang, M., Park, H. Y., Lee, S. H., Rincon, M., et al. (2013). Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung cancer. Lung Cancer 79, 198-204. doi:10.1016/j.lungcan.2012.11.019
62. Pignon, J. P., Tribodet, H., Scagliotti, G. V., Douillard, J. Y., Shepherd, F. A., Stephens, R. J., et al. (2008). Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J. Clin. Oncol. 26, 3552-3559. doi:10.1200/JCO.2007.13.9030
63. Ramalingam, S. S., Maitland, M. L., Frankel, P., Argiris, A. E., Koczywas, M., Gitlitz, B., et al. (2010). Carboplatin and paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J. Clin. Oncol. 28, 56-62. doi:10.1200/JCO.2009.24.9094
64. Rao, D. D., Vorhies, J. S., Senzer, N., and Nemunaitis, J. (2009). siRNA vs. shRNA: similarities and differences. Adv. Drug Deliv. Rev. 61, 746-759. doi:10.1016/j.addr.2009.04.004
65. Ryan, Q. C., Headlee, D., Acharya, M., Sparreboom, A., Trepel, J. B., Ye, J., et al. (2005). Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J. Clin. Oncol. 23, 3912-3922. doi:10.1200/JCO.2005.02.188
66. Schermelleh, L., Spada, F., Easwaran, H. P., Zolghadr, K., Margot, J. B., Cardoso, M. C., et al. (2005). Trapped in action: direct visualization of DNA methyltransferase activity in living cells. Nat. Methods 2, 751-756. doi:10.1038/nmeth794
67. Schrump, D. S., Fischette, M. R., Nguyen, D. M., Zhao, M., Li, X., Kunst, T. F., et al. (2006). Phase I study of decitabine-mediated gene expression in patients with cancers involving the lung, esophagus, or pleura. Clin. Cancer Res. 12, 5777-5785. doi:10.1158/1078-0432.CCR-06-0669
68. Selamat, S. A., Chung, B. S., Girard, L., Zhang, W., Zhang, Y., Campan, M., et al. (2012). Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression. Genome Res. 22, 1197-1211. doi:10.1101/gr.132662.111
69. Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaren, S., et al. (2010). A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141, 69-80. doi:10.1016/j.cell.2010.02.027
70. Shen, H., and Laird, P. W. (2013). Interplay between the cancer genome and epigenome. Cell 153, 38-55. doi:10.1016/j.cell.2013.03.008
71. Shinjo, K., Okamoto, Y., An, B., Yokoyama, T., Takeuchi, I., Fujii, M., et al. (2012). Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. Carcinogenesis 33, 1277-1285. doi:10.1093/carcin/bgs154
72. Singh, T., Prasad, R., and Katiyar, S. K. (2013). Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo. Epigenetics 8, 54-65. doi:10.4161/epi.23078
73. Stathis, A., Hotte, S. J., Chen, E. X., Hirte, H. W., Oza, A. M., Moretto, P., et al. (2011). Phase I study of decitabine in combination with vorinostat in patients with advanced solid tumors and non-Hodgkin's lymphomas. Clin. Cancer Res. 17, 1582-1590. doi:10.1158/1078-0432.CCR-10-1893
74. Strahl, B., and Allis, C. (2000). The language of covalent histone modifications. Nature 403, 41-45. doi:10.1038/47412
75. Tang, Y. A., Wen, W. L., Chang, J. W., Wei, T. T., Tan, Y. H., Salunke, S., 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 14:e12417. doi:10.1371/journal.pone.0012417
76. Tong, A. W. (2006). Small RNAs and non-small cell lung cancer. Curr. Mol. Med. 6, 339-349. doi:10.2174/156652406776894554
77. Traynor, A. M., Dubey, S., Eickhoff, J. C., Kolesar, J. M., Schell, K., Huie, M. S., et al. (2009). Vorinostat (NSC# 701852) in patients with relapsed non-small cell lung cancer: a Wisconsin Oncology Network phase II study. J. Thorac. Oncol. 4, 522-526. doi:10.1097/JTO.0b013e3181952478
78. Tsou, J. A., Galler, J. S., Siegmund, K. D., Laird, P. W., Turla, S., Cozen, W., et al. (2007). Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol. Cancer 6, 70. doi:10.1186/1476-4598-6-70
79. Tuddenham, L., Wheeler, G., Ntounia-Fousara, S., Waters, J., Hajihosseini, M. K., Clark, I., et al. (2006). The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. FEBS Lett. 580, 4214-4217. doi:10.1016/j.febslet.2006.06.080
80. Vansteenkiste, J., Van Cutsem, E., Dumez, H., Chen, C., Ricker, J. L., Randolph, S. S., et al. (2008). Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Invest. New Drugs 26, 483-488. doi:10.1007/s10637-008-9131-6
81. Varambally, S., Cao, Q., Mani, R. S., Shankar, S., Wang, X., Ateeq, B., et al. (2008). Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695-1699. doi:10.1126/science.1165395
82. Walter, K., Holcomb, T., Januario, T., Du, P., Evangelista, M., Kartha, N., et al. (2012). DNA methylation profiling defines clinically relevant biological subsets of non-small cell lung cancer. Clin. Cancer Res. 18, 2360-2373. doi:10.1158/1078-0432.CCR-11-2635-T
83. Wilkerson, M. D., Yin, X., Walter, V., Zhao, N., Cabanski, C. R., Hayward, M. C., et al. (2012). Differential pathogenesis of lung adenocarcinoma subtypes involving sequence mutations, copy number, chromosomal instability, and methylation. PLoS ONE 7:e36530. doi:10.1371/journal.pone.0036530
84. Witta, S. (2012). Histone deacetylase inhibitors in non-small-cell lung cancer. J. Thorac. Oncol. 7, S404-S406. doi:10.1097/JTO.0b013e31826df29c
85. Witta, S. E., Jotte, R. M., Konduri, K., Neubauer, M. A., Spira, A. I., Ruxer, R. L., et al. (2012). Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J. Clin. Oncol. 30, 2248-2255. doi:10.1200/JCO.2011.38.9411
86. Yanagawa, N., Tamura, G., Oizumi, H., Takahashi, N., Shimazaki, Y., and Motoyama, T. (2002). Frequent epigenetic silencing of the p16 gene in non-small cell lung cancers of tobacco smokers. Jpn. J. Cancer Res. 93, 1107-1113. doi:10.1111/j.1349-7006.2002.tb01212.x
87. Yang, X., Lay, F., Han, H., and Jones, P. A. (2010). Targeting DNA methylation for epigenetic therapy. Trends Pharmacol. Sci. 31, 536-546. doi:10.1016/j.tips.2010.08.001
88. Zhou, X. Y., Nie, C. L., Liang, S. F., Yuan, Z., Deng, H. X., and Wei, Y. Q. (2012). Enhanced gemcitabine-mediated cell killing of human lung adenocarcinoma by vector-based RNA interference against PLK1. Biomed. Pharmacother. 66, 597-602. doi:10.1016/j.biopha.2012.01.003
89. Zhu, W. G., Lakshmanan, R. R., Beal, M. D., and Otterson, G. A. (2001). DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. Cancer Res. 61, 1327-1333.
90. Zöchbauer-Muller, S., Fong, K. M., Virmani, A. K., Geradts, J., Gazdar, A. F., and Minna, J. D. (2001). Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 61, 249-255.
91. Zou, M., Xia, S., Zhuang, L., Han, N., Chu, Q., Chao, T., et al. (2013). Knockdown of the Bcl-2 gene increases sensitivity to EGFR tyrosine kinase inhibitors in the H1975 lung cancer cell line harboring T790M mutation. Int. J. Oncol. 42, 2094-2102. doi:10.3892/ijo.2013.1895
92. Zuco, V., De Cesare, M., Cincinelli, R., Nannei, R., Pisano, C., Zaffaroni, N., et al. (2011). Synergistic antitumor effects of novel HDAC inhibitors and paclitaxel in vitro and in vivo. PLoS ONE 6:e29085. doi:10.1371/journal.pone.0029085