Abstract
In last several years, the focus on the origin and progression of human cancers has shifted from genetic to epigenetic regulation, with particular attention to methylation and acetylation events that have profound effect on the eventual expression of oncogenes and the suppression of tumor suppressors. A few drugs targeting these epigenetic changes have already been approved for treatment, albeit not for lung cancer. With the recent advances in the push towards personalized therapy, questions have been asked about the possible targeting of epigenetic events for personalized lung cancer therapy. Some progress has been made but a lot needs to be done. In this chapter, a succinct review of these topics is provided.
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References
Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29
Arcaro A (2015) Targeted therapies for small cell lung cancer: where do we stand? Crit Rev Oncol Hematol 95:133–264
Esteller M (2008) Epigenetics in cancer. N Engl J Med 358(11):1148–1159
Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895):89–92
Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW et al (1983) The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res 11(19):6883–6894
Steenbergen RD, Snijders PJ, Heideman DA, Meijer CJ (2014) Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions. Nat Rev Cancer 14(6):395–405
Choi JD, Lee JS (2013) Interplay between epigenetics and genetics in cancer. Genomics Inform 11(4):164–173
Campbell RM, Tummino PJ (2014) Cancer epigenetics drug discovery and development: the challenge of hitting the mark. J Clin Invest 124(1):64–69
Heyn H, Esteller M (2012) DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet 13(10):679–692
Li J, Jin H, Wang X (2014) Epigenetic biomarkers: potential applications in gastrointestinal cancers. ISRN Gastroenterol 2014:464015
Shukla S, Meeran SM (2014) Epigenetics of cancer stem cells: pathways and therapeutics. Biochim Biophys Acta 1840(12):3494–3502
Ohnishi K, Semi K, Yamada Y (2014) Epigenetic regulation leading to induced pluripotency drives cancer development in vivo. Biochem Biophys Res Commun 455:10–15
Easwaran H, Tsai HC, Baylin SB (2014) Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol Cell 54(5):716–727
Tam WL, Weinberg RA (2013) The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med 19(11):1438–1449
Wang Y, Shang Y (2013) Epigenetic control of epithelial-to-mesenchymal transition and cancer metastasis. Exp Cell Res 319(2):160–169
Liu X, Chen X, Yu X, Tao Y, Bode AM, Dong Z et al (2013) Regulation of microRNAs by epigenetics and their interplay involved in cancer. J Exp Clin Cancer Res 32:96
Baer C, Claus R, Plass C (2013) Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res 73(2):473–477
Ahmad A, Li Y, Bao B, Kong D, Sarkar FH (2014) Epigenetic regulation of miRNA-cancer stem cells nexus by nutraceuticals. Mol Nutr Food Res 58(1):79–86
Miceli M, Bontempo P, Nebbioso A, Altucci L (2014) Natural compounds in epigenetics: a current view. Food Chem Toxicol 73c:71–83
Langevin SM, Kratzke RA, Kelsey KT (2014) Epigenetics of lung cancer. Transl Res 165:74–90
Jakopovic M, Thomas A, Balasubramaniam S, Schrump D, Giaccone G, Bates SE (2013) Targeting the epigenome in lung cancer: expanding approaches to epigenetic therapy. Front Oncol 3:261
Vandermeers F, Neelature Sriramareddy S, Costa C, Hubaux R, Cosse JP, Willems L (2013) The role of epigenetics in malignant pleural mesothelioma. Lung Cancer 81(3):311–318
Balgkouranidou I, Liloglou T, Lianidou ES (2013) Lung cancer epigenetics: emerging biomarkers. Biomark Med 7(1):49–58
Okayama H, Schetter AJ, Ishigame T, Robles A, Kohno T, Yokota J et al (2014) The expression of four genes as a prognostic classifier for stage I lung adenocarcinoma in 12 independent cohorts. Cancer Epidemiol Biomarkers Prev 23:2884–2894
Akagi I, Okayama H, Schetter AJ, Robles AI, Kohno T, Bowman ED et al (2013) Combination of protein coding and noncoding gene expression as a robust prognostic classifier in stage I lung adenocarcinoma. Cancer Res 73(13):3821–3832
Ruiz R, Raez LE, Rolfo C (2015) Entinostat (SNDX-275) for the treatment of non-small cell lung cancer. Expert Opin Investig Drugs 24:1101–1109
Falkenberg KJ, Johnstone RW (2014) Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov 13(9):673–691
Heerboth S, Lapinska K, Snyder N, Leary M, Rollinson S, Sarkar S (2014) Use of epigenetic drugs in disease: an overview. Genet Epigenet 6:9–19
Mottamal M, Zheng S, Huang TL, Wang G (2015) Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules 20(3):3898–3941
Dekker FJ, Haisma HJ (2009) Histone acetyl transferases as emerging drug targets. Drug Discov Today 14(19–20):942–948
Manzo F, Tambaro FP, Mai A, Altucci L (2009) Histone acetyltransferase inhibitors and preclinical studies. Expert Opin Ther Pat 19(6):761–774
Platta CS, Greenblatt DY, Kunnimalaiyaan M, Chen H (2007) The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. J Surg Res 142(2):219–226
Chun SM, Lee JY, Choi J, Lee JH, Hwang JJ, Kim CS et al (2015) Epigenetic modulation with HDAC inhibitor CG200745 induces anti-proliferation in non-small cell lung cancer cells. PLoS One 10(3), e0119379
Kong D, Ahmad A, Bao B, Li Y, Banerjee S, Sarkar FH (2012) Histone deacetylase inhibitors induce epithelial-to-mesenchymal transition in prostate cancer cells. PLoS One 7(9), e45045
Miozzo M, Vaira V, Sirchia SM (2015) Epigenetic alterations in cancer and personalized cancer treatment. Future Oncol 11(2):333–348
Shukla S, Khan S, Kumar S, Sinha S, Farhan M, Bora HK et al (2015) Cucurbitacin B alters the expression of tumor-related genes by epigenetic modifications in NSCLC and inhibits NNK-induced lung tumorigenesis. Cancer Prev Res (Phila) 8(6):552–562
Tang J, Xiong Y, Zhou HH, Chen XP (2014) DNA methylation and personalized medicine. J Clin Pharm Ther 39(6):621–627
Clark SJ, Statham A, Stirzaker C, Molloy PL, Frommer M (2006) DNA methylation: bisulphite modification and analysis. Nat Protoc 1(5):2353–2364
Li J, Ching T, Huang S, Garmire LX (2015) Using epigenomics data to predict gene expression in lung cancer. BMC Bioinf 16(suppl 5):S10
Kim Y, Kim DH (2015) CpG island hypermethylation as a biomarker for the early detection of lung cancer. Methods Mol Biol 1238:141–171
Khakpour G, Pooladi A, Izadi P, Noruzinia M, Tavakkoly Bazzaz J (2015) DNA methylation as a promising landscape: a simple blood test for breast cancer prediction. Tumour Biol 36:4905–4912
Volkel P, Dupret B, Le Bourhis X, Angrand PO (2015) Diverse involvement of EZH2 in cancer epigenetics. Am J Transl Res 7(2):175–193
McCabe MT, Creasy CL (2014) EZH2 as a potential target in cancer therapy. Epigenomics 6(3):341–351
Kondo Y (2014) Targeting histone methyltransferase EZH2 as cancer treatment. J Biochem 156(5):249–257
Kong D, Heath E, Chen W, Cher ML, Powell I, Heilbrun L et al (2012) Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One 7(3), e33729
Fillmore CM, Xu C, Desai PT, Berry JM, Rowbotham SP, Lin YJ et al (2015) EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors. Nature 520(7546):239–242
Wu PC, Lu JW, Yang JY, Lin IH, Ou DL, Lin YH et al (2014) H3K9 histone methyltransferase, KMT1E/SETDB1, cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis. Cancer Res 74(24):7333–7343
Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129(4):823–837
Falahi F, Sgro A, Blancafort P (2015) Epigenome engineering in cancer: fairytale or a realistic path to the clinic? Front Oncol 5:22
Dai SP, Xie C, Ding N, Zhang YJ, Han L, Han YW (2015) Targeted inhibition of genome-wide DNA methylation analysis in epigenetically modulated phenotypes in lung cancer. Med Oncol 32(6):615
Bulk E, Ay AS, Hammadi M, Ouadid-Ahidouch H, Schelhaas S, Hascher A et al (2015) Epigenetic dysregulation of K 3.1 channels induces poor prognosis in lung cancer. Int J Cancer 137:1306–1317
Mansfield AS, Wang L, Cunningham JM, Jen J, Kolbert CP, Sun Z et al (2015) DNA methylation and RNA expression profiles in lung adenocarcinomas of never-smokers. Cancer Genet 208(5):253–260
Soes S, Daugaard IL, Sorensen BS, Carus A, Mattheisen M, Alsner J et al (2014) Hypomethylation and increased expression of the putative oncogene ELMO3 are associated with lung cancer development and metastases formation. Oncoscience 1(5):367–374
Barrow TM, Michels KB (2014) Epigenetic epidemiology of cancer. Biochem Biophys Res Commun 455:70–83
Belinsky SA, Liechty KC, Gentry FD, Wolf HJ, 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(6):3338–3344
Cirincione R, Lintas C, Conte D, Mariani L, Roz L, Vignola AM et al (2006) Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: a nested case-control study. Int J Cancer 118(5):1248–1253
Lou-Qian Z, Rong Y, Ming L, Xin Y, Feng J, Lin X (2013) The prognostic value of epigenetic silencing of p16 gene in NSCLC patients: a systematic review and meta-analysis. PLoS One 8(1), e54970
Miao Y, Wang L, Zhang X, Xu X, Jiang G, Fan C et al (2014) Promoter methylation-mediated silencing of beta-catenin enhances invasiveness of non-small cell lung cancer and predicts adverse prognosis. PLoS One 9(11), e112258
Xue R, Yang C, Zhao F, Li D (2014) Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC. Onco Targets Ther 7:1987–1996
Shi M, Wang S, Yao Y, Li Y, Zhang H, Han F et al (2014) Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer. Sci Rep 4:7545
Liu WB, Han F, Jiang X, Chen HQ, Zhao H, Liu Y et al (2015) TMEM196 acts as a novel functional tumour suppressor inactivated by DNA methylation and is a potential prognostic biomarker in lung cancer. Oncotarget 6:21225–21239
Rhee YY, Lee TH, Song YS, Wen X, Kim H, Jheon S et al (2015) Prognostic significance of promoter CpG island hypermethylation and repetitive DNA hypomethylation in stage I lung adenocarcinoma. Virchows Arch 466(6):675–683
Zhou C, Qin Y, Xie Z, Zhang J, Yang M, Li S et al (2015) NPTX1 is a novel epigenetic regulation gene and associated with prognosis in lung cancer. Biochem Biophys Res Commun 458(2):381–386
Li N, Li S (2015) Epigenetic inactivation of SOX1 promotes cell migration in lung cancer. Tumour Biol 36:4603–4610
Li W, Deng J, Wang SS, Ma L, Pei J, Zeng XX et al (2014) Association of methylation of the RAR-beta gene with cigarette smoking in non-small cell lung cancer with Southern-Central Chinese population. Asian Pac J Cancer Prev 15(24):10937–10941
Avila-Moreno F, Armas-Lopez L, Alvarez-Moran AM, Lopez-Bujanda Z, Ortiz-Quintero B, Hidalgo-Miranda A et al (2014) Overexpression of MEOX2 and TWIST1 is associated with H3K27me3 levels and determines lung cancer chemoresistance and prognosis. PLoS One 9(12), e114104
Zuco V, Cassinelli G, Cossa G, Gatti L, Favini E, Tortoreto M et al (2015) Targeting the invasive phenotype of cisplatin-resistant non-small cell lung cancer cells by a novel histone deacetylase inhibitor. Biochem Pharmacol 94(2):79–90
El-Awady RA, Herzi F, Al-Tunaiji H, Saleh EM, Abdel-Wahab AH, Al Homssi A et al (2015) Epigenetics and miRNA as predictive markers and targets for lung cancer chemotherapy. Cancer Biol Ther 16:1056–1070
Tao L, Huang G, Chen Y, Chen L (2015) DNA methylation of DKK3 modulates docetaxel chemoresistance in human nonsmall cell lung cancer cell. Cancer Biother Radiopharm 30(2):100–106
Vendetti FP, Topper M, Huang P, Dobromilskaya I, Easwaran H, Wrangle J et al (2015) Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget 6(1):56–70
Shenker NS, Polidoro S, van Veldhoven K, Sacerdote C, Ricceri F, Birrell MA et al (2013) Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet 22(5):843–851
Shenker NS, Ueland PM, Polidoro S, van Veldhoven K, Ricceri F, Brown R et al (2013) DNA methylation as a long-term biomarker of exposure to tobacco smoke. Epidemiology 24(5):712–716
Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH et al (2009) Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 179(7):572–578
Belinsky SA (2015) Unmasking the lung cancer epigenome. Annu Rev Physiol 77:453–474
Hamm CA, Costa FF (2015) Epigenomes as therapeutic targets. Pharmacol Ther 151:72–86
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Ahmad, A. (2016). Epigenetics in Personalized Management of Lung Cancer. In: Ahmad, A., Gadgeel, S. (eds) Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. Advances in Experimental Medicine and Biology, vol 890. Springer, Cham. https://doi.org/10.1007/978-3-319-24932-2_6
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DOI: https://doi.org/10.1007/978-3-319-24932-2_6
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