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2000
Volume 25, Issue 8
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Epigenetic mechanisms have been shown to play a critical role in the development and progression of gastrointestinal [GI] cancers. These mechanisms involve modifications to DNA and histones that can alter gene expression patterns and may contribute to the initiation and progression of cancers. In recent years, epigenetic therapies have emerged as a promising approach to treating GI cancers. These therapies target specific epigenetic modifications, such as DNA methylation and histone acetylation, to restore normal gene expression patterns and inhibit cancer cell growth. Several epigenetic drugs have been approved for the treatment of GI cancers. Moreover, the use of epigenetic therapies in combination with other treatments, such as chemotherapeutic agents, is being studied to improve treatment outcomes.

We have provided an overview of the role of epigenetic mechanisms in GI cancer treatment aimed to focus on recent evidence of the use of epigenetic agents in clinical and preclinical GI cancer studies, including gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Overall, the role of epigenetic mechanisms in GI cancer treatments is an active area of research with the potential to improve patients' treatment outcomes and advance cancer treatment strategies.

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References

  1. SchillerJT LowyDR Virus infection and human cancer: An overview.Recent Results Cancer Res201419311010.1007/978‑3‑642‑38965‑8_1
     [Google Scholar]
  2. SiegelR.L. MillerK.D. JemalA. Cancer statistics, 2018.CA Cancer J. Clin.201868173010.3322/caac.2144229313949
     [Google Scholar]
  3. PatelA. Benign vs malignant tumors.JAMA Oncol.202069148810.1001/jamaoncol.2020.259232729930
     [Google Scholar]
  4. ColliL.M. MachielaM.J. ZhangH. MyersT.A. JessopL. DelattreO. YuK. ChanockS.J. Landscape of combination immunotherapy and targeted therapy to improve cancer management.Cancer Res.201777133666367110.1158/0008‑5472.CAN‑16‑333828446466
     [Google Scholar]
  5. SchirrmacherV. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review).Int. J. Oncol.201854240741910.3892/ijo.2018.466130570109
     [Google Scholar]
  6. LerutT. CoosemansW. DeckerG. De LeynP. MoonsJ. NafteuxP. Van RaemdonckD. Surgical techniques.J. Surg. Oncol.200592321822910.1002/jso.2036316299783
     [Google Scholar]
  7. HanahanD WeinbergRA Hallmarks of cancer: The next generation.cell20111445646674
     [Google Scholar]
  8. Rodríguez-ParedesM. EstellerM. Cancer epigenetics reaches mainstream oncology.Nat. Med.201117333033910.1038/nm.230521386836
     [Google Scholar]
  9. DawsonMA KouzaridesT Cancer epigenetics: From mechanism to therapy.cell201215011227
     [Google Scholar]
  10. FeinbergA.P. Phenotypic plasticity and the epigenetics of human disease.Nature2007447714343344010.1038/nature0591917522677
     [Google Scholar]
  11. NovakK. Epigenetics changes in cancer cells.Med.Gen.Med.20046417
     [Google Scholar]
  12. EstellerM. Epigenetic changes in cancer.F1000 Biol. Rep.20113910.3410/B3‑921655338
     [Google Scholar]
  13. FeinbergA.P. The key role of epigenetics in human disease prevention and mitigation.N. Engl. J. Med.2018378141323133410.1056/NEJMra140251329617578
     [Google Scholar]
  14. TollefsbolT. Handbook of epigenetics: the new molecular and medical genetics.Academic Press2017
     [Google Scholar]
  15. DrakeT.M. SøreideK. Cancer epigenetics in solid organ tumours: A primer for surgical oncologists.Eur. J. Surg. Oncol.201945573674610.1016/j.ejso.2019.02.00530745135
     [Google Scholar]
  16. YouJ.S. JonesP.A. Cancer genetics and epigenetics: two sides of the same coin?Cancer Cell201222192010.1016/j.ccr.2012.06.00822789535
     [Google Scholar]
  17. ShenH. LairdP.W. Interplay between the cancer genome and epigenome.Cell20131531385510.1016/j.cell.2013.03.00823540689
     [Google Scholar]
  18. SceusiE.L. LooseD.S. WrayC.J. Clinical implications of DNA methylation in hepatocellular carcinoma.HPB201113636937610.1111/j.1477‑2574.2011.00303.x21609368
     [Google Scholar]
  19. WeberM. HellmannI. StadlerM.B. RamosL. PääboS. RebhanM. SchübelerD. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome.Nat. Genet.200739445746610.1038/ng199017334365
     [Google Scholar]
  20. WahidB AliA RafiqueS IdreesM New insights into the epigenetics of hepatocellular carcinoma.Biomed Res Int20172017160957510.1155/2017/1609575
     [Google Scholar]
  21. BjornssonH. FallinM.D. FeinbergA.P. An integrated epigenetic and genetic approach to common human disease.Trends Genet.200420835035810.1016/j.tig.2004.06.00915262407
     [Google Scholar]
  22. EstellerM. CornP.G. BaylinS.B. HermanJ.G. A gene hypermethylation profile of human cancer.Cancer Res.20016183225322911309270
     [Google Scholar]
  23. JonesP.A. BaylinS.B. The fundamental role of epigenetic events in cancer.Nat. Rev. Genet.20023641542810.1038/nrg81612042769
     [Google Scholar]
  24. BhasinM. ReinherzE.L. RecheP.A. Recognition and classification of histones using support vector machine.J. Comput. Biol.200613110211210.1089/cmb.2006.13.10216472024
     [Google Scholar]
  25. PetersonC.L. LanielM.A. Histones and histone modifications.Curr. Biol.20041414R546R55110.1016/j.cub.2004.07.00715268870
     [Google Scholar]
  26. SharmaS. KellyT.K. JonesP.A. Epigenetics in cancer.Carcinogenesis2010311273610.1093/carcin/bgp22019752007
     [Google Scholar]
  27. González-RamírezI. Soto-ReyesE. Sánchez-PérezY. HerreraL.A. García-CuellarC. Histones and long non-coding RNAs: The new insights of epigenetic deregulation involved in oral cancer.Oral Oncol.201450869169510.1016/j.oraloncology.2014.04.00624844984
     [Google Scholar]
  28. AlamH. GuB. LeeM.G. Histone methylation modifiers in cellular signaling pathways.Cell. Mol. Life Sci.201572234577459210.1007/s00018‑015‑2023‑y26305020
     [Google Scholar]
  29. BaylinS.B. JonesP.A. A decade of exploring the cancer epigenome biological and translational implications.Nat. Rev. Cancer2011111072673410.1038/nrc313021941284
     [Google Scholar]
  30. CedarH. BergmanY. Linking DNA methylation and histone modification: patterns and paradigms.Nat. Rev. Genet.200910529530410.1038/nrg254019308066
     [Google Scholar]
  31. WangL. MengD. WangY. HuJ. Long non-coding RNA LINC01296 promotes esophageal squamous cell carcinoma cell proliferation and invasion by epigenetic suppression of KLF2.Am. J. Cancer Res.20188102020202930416853
     [Google Scholar]
  32. WangZ. LiX. The role of noncoding RNA in hepatocellular carcinoma.Gland Surg.201321252925083452
     [Google Scholar]
  33. GeorgeJ. PatelT. Noncoding RNA as therapeutic targets for hepatocellular carcinoma.Seminars in liver disease.Thieme Medical Publishers2015
     [Google Scholar]
  34. CostaF.F. Non-coding RNAs: New players in eukaryotic biology.Gene20053572839410.1016/j.gene.2005.06.01916111837
     [Google Scholar]
  35. PonjavicJ. PontingC.P. LunterG. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs.Genome Res.200717555656510.1101/gr.603680717387145
     [Google Scholar]
  36. XiaoY. SuM. OuW. WangH. TianB. MaJ. TangJ. WuJ. WuZ. WangW. ZhouY. Involvement of noncoding RNAs in epigenetic modifications of esophageal cancer.Biomed. Pharmacother.201911710919210.1016/j.biopha.2019.10919231387188
     [Google Scholar]
  37. AnastasiadouE. JacobL.S. SlackF.J. Non-coding RNA networks in cancer.Nat. Rev. Cancer201818151810.1038/nrc.2017.9929170536
     [Google Scholar]
  38. RathinasamyB. VelmuruganB.K. Role of lncRNAs in the cancer development and progression and their regulation by various phytochemicals.Biomed. Pharmacother.201810224224810.1016/j.biopha.2018.03.07729567536
     [Google Scholar]
  39. Martín-SuberoJI EstellerM Epigenetic mechanisms in cancer development. ColemanW. TsongalisG. The Molecular Basis of Human CancerHumana PressNew York, NY201726327510.1007/978‑1‑59745‑458‑2_16
     [Google Scholar]
  40. BandresE. AgirreX. BitarteN. RamirezN. ZarateR. Roman-GomezJ. ProsperF. Garcia-FoncillasJ. Epigenetic regulation of microRNA expression in colorectal cancer.Int. J. Cancer2009125112737274310.1002/ijc.2463819521961
     [Google Scholar]
  41. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
     [Google Scholar]
  42. SmythE.C. LagergrenJ. FitzgeraldR.C. LordickF. ShahM.A. LagergrenP. CunninghamD. Oesophageal cancer.Nat. Rev. Dis. Primers2017311704810.1038/nrdp.2017.4828748917
     [Google Scholar]
  43. KhalafiS. LockhartA.C. LivingstoneA.S. El-RifaiW. Targeted molecular therapies in the treatment of esophageal adenocarcinoma, are we there yet?Cancers20201211307710.3390/cancers1211307733105560
     [Google Scholar]
  44. ColemanH.G. XieS.H. LagergrenJ. The epidemiology of esophageal adenocarcinoma.Gastroenterology2018154239040510.1053/j.gastro.2017.07.04628780073
     [Google Scholar]
  45. ZhangY. LiuS. ZhouS. YuD. GuJ. QinQ. ChengY. SunX. Focal adhesion kinase: Insight into its roles and therapeutic potential in oesophageal cancer.Cancer Lett.20214969310310.1016/j.canlet.2020.10.00533038490
     [Google Scholar]
  46. ZhangR. JiaM. LiP. HanJ. HuangK. LiQ. QiaoY. XuT. RuanP. HuQ. FanG. SongQ. FuZ. Radiotherapy improves the survival of patients with metastatic esophageal squamous cell carcinoma: A propensity score matched analysis of Surveillance, Epidemiology, and End Results database.Dis. Esophagus2019321doy07410.1093/dote/doy07430277502
     [Google Scholar]
  47. MaK. CaoB. GuoM. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma.Clin. Epigenetics2016814310.1186/s13148‑016‑0210‑927110300
     [Google Scholar]
  48. GuoM. RenJ. HouseM.G. QiY. BrockM.V. HermanJ.G. Accumulation of promoter methylation suggests epigenetic progression in squamous cell carcinoma of the esophagus.Clin. Cancer Res.200612154515452210.1158/1078‑0432.CCR‑05‑285816899597
     [Google Scholar]
  49. PauliA. RinnJ.L. SchierA.F. Non-coding RNAs as regulators of embryogenesis.Nat. Rev. Genet.201112213614910.1038/nrg290421245830
     [Google Scholar]
  50. WongN.A.C.S. WildingJ. BartlettS. LiuY. WarrenB.F. PirisJ. MaynardN. MarshallR. BodmerW.F. CDX1 is an important molecular mediator of Barrett’s metaplasia.Proc. Natl. Acad. Sci.2005102217565757010.1073/pnas.050203110215894614
     [Google Scholar]
  51. ShibagakiI. ShimadaY. WagataT. IkenagaM. ImamuraM. IshizakiK. Allelotype analysis of esophageal squamous cell carcinoma.Cancer Res.19945411299630008187088
     [Google Scholar]
  52. BaffaR. NegriniM. MandesB. RuggeM. RanzaniG.N. HirohashiS. CroceC.M. Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach.Cancer Res.19965622682728542579
     [Google Scholar]
  53. SoejimaH. NakagawachiT. ZhaoW. HigashimotoK. UranoT. MatsukuraS. KitajimaY. TakeuchiM. NakayamaM. OshimuraM. MiyazakiK. JohK. MukaiT. Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer.Oncogene200423254380438810.1038/sj.onc.120757615007390
     [Google Scholar]
  54. KlumpB. HsiehC.J. HolzmannK. GregorM. PorschenR. Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett’s esophagus.Gastroenterology199811561381138610.1016/S0016‑5085(98)70016‑29834265
     [Google Scholar]
  55. SarbiaM. GeddertH. KlumpB. KielS. IskenderE. GabbertH.E. Hypermethylation of tumor suppressor genes ( p16 INK4A , p14 ARF and APC ) in adenocarcinomas of the upper gastrointestinal tract.Int. J. Cancer2004111222422810.1002/ijc.2021215197775
     [Google Scholar]
  56. MaesawaC. TamuraG. NishizukaS. OgasawaraS. IshidaK. TerashimaM. SakataK. SatoN. SaitoK. SatodateR. Inactivation of the CDKN2 gene by homozygous deletion and de novo methylation is associated with advanced stage esophageal squamous cell carcinoma.Cancer Res.19965617387538788752149
     [Google Scholar]
  57. KwongF.M. TangJ.C.O. SrivastavaG. LungM.L. Inactivation mechanisms and growth suppressive effects of p16INK4a in Asian esophageal squamous carcinoma cell lines.Cancer Lett.2004208220721310.1016/j.canlet.2003.11.01715142680
     [Google Scholar]
  58. HardieL.J. DarntonS.J. WallisY.L. ChauhanA. HainautP. WildC.P. CassonA.G. p16 expression in Barrett’s esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations.Cancer Lett.2005217222123010.1016/j.canlet.2004.06.02515617840
     [Google Scholar]
  59. ClémentG BraunschweigR PasquierN BosmanFT BenhattarJ Methylation of APC, TIMP3, and TERT: A new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation.J Pathol20062081100107
     [Google Scholar]
  60. TanakaH. ShimadaY. HaradaH. ShinodaM. HatookaS. ImamuraM. IshizakiK. Methylation of the 5′ CpG island of the FHIT gene is closely associated with transcriptional inactivation in esophageal squamous cell carcinomas.Cancer Res.19985815342934349699676
     [Google Scholar]
  61. KurokiT. TrapassoF. YendamuriS. MatsuyamaA. AlderH. MoriM. CroceC.M. Allele loss and promoter hypermethylation of VHL, RAR-β, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma.Cancer Res.200363133724372812839965
     [Google Scholar]
  62. ZhaoR. CassonA. Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer.Curr. Cancer Drug Targets20088650952110.2174/15680090878569930618781897
     [Google Scholar]
  63. SchildhausH.U. KröckelI. LippertH. MalfertheinerP. RoessnerA. Schneider-StockR. Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach.Int. J. Oncol.20052661493150010.3892/ijo.26.6.149315870861
     [Google Scholar]
  64. BaumannS. KellerG. PühringerF. NapieralskiR. FeithM. LangerR. HöflerH. SteinH.J. SarbiaM. The prognostic impact of O 6 ‐Methylguanine‐DNA Methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma.Int. J. Cancer2006119226426810.1002/ijc.2184816477636
     [Google Scholar]
  65. FangM.Z. JinZ. WangY. LiaoJ. YangG.Y. WangL.D. YangC. Promoter hypermethylation and inactivation of O6-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines.Int. J. Oncol.200526361562210.3892/ijo.26.3.61515703815
     [Google Scholar]
  66. PorsK. PattersonL. DNA mismatch repair deficiency, resistance to cancer chemotherapy and the development of hypersensitive agents.Curr. Top. Med. Chem.20055121133114910.2174/15680260577437088316248788
     [Google Scholar]
  67. TzaoC HsuH-S SunG-H LaiH-L WangY-C TungH-J Promoter methylation of the hMLH1 gene and protein expression of human mutL homolog 1 and human mutS homolog 2 in resected esophageal squamous cell carcinoma.J Thorac Cardiovasc Surg20051305137110.1016/j.jtcvs.2005.06.004
     [Google Scholar]
  68. ZhangG.Y. MaC.X. LiuQ.L. LeX.P. DingY. ZhangQ.X. Detection of methylation of hMSH2 gene promoter region of esophageal cancer.Chin.J. Oncol.200527954154316438852
     [Google Scholar]
  69. ClémentG. BraunschweigR. PasquierN. BosmanF.T. BenhattarJ. Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett’s esophagus.Oncogene200625213084309210.1038/sj.onc.120933816407829
     [Google Scholar]
  70. TakenoS. NoguchiT. FumotoS. KimuraY. ShibataT. KawaharaK. E-cadherin expression in patients with esophageal squamous cell carcinoma: promoter hypermethylation, Snail overexpression, and clinicopathologic implications.Am. J. Clin. Pathol.20041221788410.1309/WJL90JPEM17RBUHT15272533
     [Google Scholar]
  71. DarntonS.J. HardieL.J. MucR.S. WildC.P. CassonA.G. Tissue inhibitor of metalloproteinase‐3 ( TIMP‐3 ) gene is methylated in the development of esophageal adenocarcinoma: Loss of expression correlates with poor prognosis.Int. J. Cancer2005115335135810.1002/ijc.2083015688381
     [Google Scholar]
  72. KuesterD. DarA.A. MoskalukC.C. KruegerS. MeyerF. HartigR. StolteM. MalfertheinerP. LippertH. RoessnerA. El-RifaiW. Schneider-StockR. Early involvement of death-associated protein kinase promoter hypermethylation in the carcinogenesis of Barrett’s esophageal adenocarcinoma and its association with clinical progression.Neoplasia20079323624510.1593/neo.0680217401463
     [Google Scholar]
  73. MaityA.K. StoneT.C. WardV. WebsterA.P. YangZ. HoganA. McBainH. DukuM. HoK.M.A. WolfsonP. GrahamD.G. BeckS. TeschendorffA.E. LovatL.B. Novel epigenetic network biomarkers for early detection of esophageal cancer.Clin. Epigenetics20221412310.1186/s13148‑022‑01243‑535164838
     [Google Scholar]
  74. SaltaS. Macedo-SilvaC. Miranda-GonçalvesV. LopesN. GiglianoD. GuimarãesR. FarinhaM. SousaO. HenriqueR. JerónimoC. A DNA methylation-based test for esophageal cancer detection.Biomark. Res.2020816810.1186/s40364‑020‑00248‑733292587
     [Google Scholar]
  75. TzaoC. SunG.H. TungH.J. HsuH.S. HsuW.H. WangY.C. ChengY.L. LeeS.C. Reduced acetylated histone H4 is associated with promoter methylation of the fragile histidine triad gene in resected esophageal squamous cell carcinoma.Ann. Thorac. Surg.200682239640110.1016/j.athoracsur.2006.03.06616863736
     [Google Scholar]
  76. TohY. YamamotoM. EndoK. IkedaY. BabaH. KohnoeS. YonemasuH. HachitandaY. OkamuraT. SugimachiK. Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma.Oncol. Rep.200310233333810.3892/or.10.2.33312579268
     [Google Scholar]
  77. TohY. OhgaT. EndoK. AdachiE. KusumotoH. HaraguchiM. OkamuraT. NicolsonG.L. Expression of the metastasis‐associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas.Int. J. Cancer2004110336236710.1002/ijc.2015415095300
     [Google Scholar]
  78. ChenC. ZhaoM. YinN. HeB. WangB. YuanY. YuF. HuJ. YinB. LuQ. Abnormal histone acetylation and methylation levels in esophageal squamous cell carcinomas.Cancer Invest.201129854855610.3109/07357907.2011.59781021843048
     [Google Scholar]
  79. SchizasD. MastorakiA. NaarL. SpartalisE. TsilimigrasD.I. KarachaliouG.S. BagiasG. MorisD. Concept of histone deacetylases in cancer: Reflections on esophageal carcinogenesis and treatment.World J. Gastroenterol.201824414635464210.3748/wjg.v24.i41.463530416311
     [Google Scholar]
  80. KongK.L. KwongD.L.W. ChanT.H.M. LawS.Y.K. ChenL. LiY. QinY.R. GuanX.Y. MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor.Gut2012611334210.1136/gutjnl‑2011‑30017821813472
     [Google Scholar]
  81. ZhangN. FuH. SongL. DingY. WangX. ZhaoC. ZhaoY. JiaoF. ZhaoY. MicroRNA-100 promotes migration and invasion through mammalian target of rapamycin in esophageal squamous cell carcinoma.Oncol. Rep.20143241409141810.3892/or.2014.338925109390
     [Google Scholar]
  82. SuM. XiaoY. MaJ. CaoD. ZhouY. WangH. LiaoQ. WangW. Long non-coding RNAs in esophageal cancer: Molecular mechanisms, functions, and potential applications.J. Hematol. Oncol.201811111810.1186/s13045‑018‑0663‑830223861
     [Google Scholar]
  83. ZhouX.L. WangW.W. ZhuW.G. YuC.H. TaoG.Z. WuQ.Q. SongY.Q. PanP. TongY.S. High expression of long non‐coding RNA AFAP1‐AS1 predicts chemoradioresistance and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.Mol. Carcinog.201655122095210510.1002/mc.2245426756568
     [Google Scholar]
  84. WangW. ZhuY. LiS. ChenX. JiangG. ShenZ. QiaoY. WangL. ZhengP. ZhangY. Long noncoding RNA MALAT1 promotes malignant development of esophageal squamous cell carcinoma by targeting β-catenin via Ezh2.Oncotarget2016718256682568210.18632/oncotarget.825727015363
     [Google Scholar]
  85. MorganE. SoerjomataramI. RumgayH. ColemanH.G. ThriftA.P. VignatJ. LaversanneM. FerlayJ. ArnoldM. The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: New estimates from globocan 2020.Gastroenterology20221633649658.e210.1053/j.gastro.2022.05.05435671803
     [Google Scholar]
  86. LiuW.J. ZhaoY. ChenX. MiaoM.L. ZhangR.Q. Epigenetic modifications in esophageal cancer: An evolving biomarker.Front. Genet.202313108747910.3389/fgene.2022.108747936704345
     [Google Scholar]
  87. MorelD. JefferyD. AspeslaghS. AlmouzniG. Postel-VinayS. Combining epigenetic drugs with other therapies for solid tumours past lessons and future promise.Nat. Rev. Clin. Oncol.20201729110710.1038/s41571‑019‑0267‑431570827
     [Google Scholar]
  88. ChangW.L. HsiehC.H. KuoI.Y. LinC.H. HuangY.L. WangY.C. Nutlin‐3 acts as a DNA methyltransferase inhibitor to sensitize esophageal cancer to chemoradiation.Mol. Carcinog.202362227728710.1002/mc.2348536342355
     [Google Scholar]
  89. AhrensT.D. TimmeS. HoeppnerJ. OstendorpJ. HembachS. FolloM. HoptU.T. WernerM. BuschH. BoerriesM. LassmannS. Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine.Epigenetics201510543144510.1080/15592294.2015.103921625923331
     [Google Scholar]
  90. ShiX. ChenX. FangB. PingY. QinG. YueD. LiF. YangS. ZhangY. Decitabine enhances tumor recognition by T cells through upregulating the MAGE-A3 expression in esophageal carcinoma.Biomed. Pharmacother.201911210863210.1016/j.biopha.2019.10863230797153
     [Google Scholar]
  91. LiuW. SangM. HouS. ZhangC. ShanB. Low-dose decitabine induces MAGE-A expression and inhibits invasion via suppression of NF-κB2 and MMP2 in Eca109 cells.Biomed. Pharmacother.201468674575010.1016/j.biopha.2014.07.01325123082
     [Google Scholar]
  92. HoshinoI. MatsubaraH. HanariN. MoriM. NishimoriT. YoneyamaY. AkutsuY. SakataH. MatsushitaK. SekiN. OchiaiT. Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells.Clin. Cancer Res.200511217945795210.1158/1078‑0432.CCR‑05‑084016278420
     [Google Scholar]
  93. FeingoldP.L. SurmanD.R. BrownK. XuY. McDuffieL.A. ShuklaV. ReardonE.S. CrooksD.R. TrepelJ.B. LeeS. LeeM.J. GaoS. XiS. McLoughlinK.C. DiggsL.P. BeerD.G. NancarrowD.J. NeckersL.M. DavisJ.L. HoangC.D. HernandezJ.M. SchrumpD.S. RipleyR.T. Induction of thioredoxin-interacting protein by a histone deacetylase inhibitor, entinostat, is associated with DNA damage and apoptosis in esophageal adenocarcinoma.Mol. Cancer Ther.20181792013202310.1158/1535‑7163.MCT‑17‑124029934340
     [Google Scholar]
  94. HuangX.P. LiX. SituM.Y. HuangL.Y. WangJ.Y. HeT.C. YanQ.H. XieX.Y. ZhangY.J. GaoY.H. LiY.H. RongT.H. WangM.R. CaiQ.Q. FuJ.H. Entinostat reverses cisplatin resistance in esophageal squamous cell carcinoma via down-regulation of multidrug resistance gene 1.Cancer Lett.201841429430010.1016/j.canlet.2017.10.02329107111
     [Google Scholar]
  95. HochhauserD. Glynne-JonesR. PotterV. GrávalosC. DoyleT.J. PathirajaK. ZhangQ. ZhangL. SausvilleE.A. A phase II study of temozolomide in patients with advanced aerodigestive tract and colorectal cancers and methylation of the O6-methylguanine-DNA methyltransferase promoter.Mol. Cancer Ther.201312580981810.1158/1535‑7163.MCT‑12‑071023443801
     [Google Scholar]
  96. SchneiderB.J. ShahM.A. KluteK. OceanA. PopaE. AltorkiN. LiebermanM. SchreinerA. YantissR. ChristosP.J. PalmerR. YouD. VialeA. KermaniP. ScanduraJ.M. Phase I study of epigenetic priming with azacitidine prior to standard neoadjuvant chemotherapy for patients with resectable gastric and esophageal adenocarcinoma: Evidence of tumor hypomethylation as an indicator of major histopathologic response.Clin. Cancer Res.201723112673268010.1158/1078‑0432.CCR‑16‑189627836862
     [Google Scholar]
  97. ChenM. NieJ. LiuY. LiX. ZhangY. BrockM.V. FengK. WuZ. LiX. ShiL. LiS. GuoM. MeiQ. HanW. Phase Ib/II study of safety and efficacy of low‐dose decitabine‐primed chemoimmunotherapy in patients with drug‐resistant relapsed/refractory alimentary tract cancer.Int. J. Cancer201814361530154010.1002/ijc.3153129663379
     [Google Scholar]
  98. SharmaP. SharmaR. miRNA–mRNA crosstalk in esophageal cancer: From diagnosis to therapy.Crit. Rev. Oncol. Hematol.201596344946210.1016/j.critrevonc.2015.07.00226257289
     [Google Scholar]
  99. RaufA. ImranM. ButtM.S. NadeemM. PetersD.G. MubarakM.S. Resveratrol as an anti-cancer agent: A review.Crit. Rev. Food Sci. Nutr.20185891428144710.1080/10408398.2016.126359728001084
     [Google Scholar]
  100. Macedo-SilvaC. ConstâncioV. Miranda-GonçalvesV. Leite-SilvaP. SaltaS. LoboJ. GuimarãesR. Carvalho-MaiaC. GiglianoD. FarinhaM. SousaO. HenriqueR. JerónimoC. DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation.Cancer Med.20231278777878810.1002/cam4.562336670548
     [Google Scholar]
  101. DimitroulisD. DamaskosC. ValsamiS. DavakisS. GarmpisN. SpartalisE. AthanasiouA. MorisD. SakellariouS. KykalosS. TsourouflisG. GarmpiA. DelladetsimaI. KontzoglouK. KouraklisG. From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world.World J. Gastroenterol.201723295282529410.3748/wjg.v23.i29.528228839428
     [Google Scholar]
  102. RassameehiranS. PatilR. PatelR. SoodG.K. Risk of HCC in HCV related cirrhosis after HCV clearance with direct acting antivirals: A systematic review and meta-analysis.Gastroenterology20171525S116310.1016/S0016‑5085(17)33892‑1
     [Google Scholar]
  103. WengM.W. LeeH.W. ChoiB. WangH.T. HuY. MehtaM. DesaiD. AminS. ZhengY. TangM.S. AFB1 hepatocarcinogenesis is via lipid peroxidation that inhibits DNA repair, sensitizes mutation susceptibility and induces aldehyde-DNA adducts at p53 mutational hotspot codon 249.Oncotarget2017811182131822610.18632/oncotarget.1531328212554
     [Google Scholar]
  104. JiangY. ChenJ. YueC. ZhangH. TongJ. LiJ. ChenT. The role of miR-182-5p in hepatocarcinogenesis of trichloroethylene in mice.Toxicol. Sci.2017156120821628013219
     [Google Scholar]
  105. HuangP-H. LuP-J. DingL-Y. ChuP-C. HsuW-Y. ChenC-S. TsaoC-C. ChenB-H. LeeC-T. ShanY-S. ChenC-S. TGFβ promotes mesenchymal phenotype of pancreatic cancer cells, in part, through epigenetic activation of VAV1.Oncogene201736162202221410.1038/onc.2016.37827893715
     [Google Scholar]
  106. ChenP. WangF. FengJ. ZhouR. ChangY. LiuJ. ZhaoQ. Co-expression network analysis identified six hub genes in association with metastasis risk and prognosis in hepatocellular carcinoma.Oncotarget2017830489484895810.18632/oncotarget.1689628430663
     [Google Scholar]
  107. FanC. KamS. RamadoriP. Metabolism-associated epigenetic and immunoepigenetic reprogramming in liver cancer.Cancers20211320525010.3390/cancers1320525034680398
     [Google Scholar]
  108. FanSY EiserC HoMC Health-related quality of life in patients with hepatocellular carcinoma: A systematic review.Clin Gastroenterol Hepatol20108755956410.1016/j.cgh.2010.03.008
     [Google Scholar]
  109. FirkinsJ.L. TarterR. DriessnackM. HansenL. A closer look at quality of life in the hepatocellular carcinoma literature.Qual. Life Res.20213061525153510.1007/s11136‑021‑02789‑233625648
     [Google Scholar]
  110. LaubeR. SabihA.H. StrasserS.I. LimL. CigoliniM. LiuK. Palliative care in hepatocellular carcinoma.J. Gastroenterol. Hepatol.202136361862810.1111/jgh.1516932627853
     [Google Scholar]
  111. Hernandez-VargasH. LambertM.P. Le Calvez-KelmF. GouysseG. McKay-ChopinS. TavtigianS.V. ScoazecJ.Y. HercegZ. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.PLoS One201053e974910.1371/journal.pone.000974920305825
     [Google Scholar]
  112. SongM.A. TiirikainenM. KweeS. OkimotoG. YuH. WongL.L. Elucidating the landscape of aberrant DNA methylation in hepatocellular carcinoma.PLoS One201382e5576110.1371/journal.pone.005576123437062
     [Google Scholar]
  113. ShenJ. WangS. ZhangY.J. KappilM. WuH.C. KibriyaM.G. WangQ. JasmineF. AhsanH. LeeP.H. YuM.W. ChenC.J. SantellaR.M. Genome-wide DNA methylation profiles in hepatocellular carcinoma.Hepatology20125561799180810.1002/hep.2556922234943
     [Google Scholar]
  114. MaL. ChuaM-S. AndrisaniO. SoS. Epigenetics in hepatocellular carcinoma: An update and future therapy perspectives.World J. Gastroenterol.201420233334510.3748/wjg.v20.i2.33324574704
     [Google Scholar]
  115. AnwarS.L. LehmannU. DNA methylation, microRNAs, and their crosstalk as potential biomarkers in hepatocellular carcinoma.World J. Gastroenterol.201420247894791310.3748/wjg.v20.i24.789424976726
     [Google Scholar]
  116. WuZ.H. YangD.L. WangL. LiuJ. Epigenetic and immune-cell infiltration changes in the tumor microenvironment in hepatocellular carcinoma.Front. Immunol.20211279334310.3389/fimmu.2021.79334334925377
     [Google Scholar]
  117. LiuG.M. ZengH.D. ZhangC.Y. XuJ.W. Identification of METTL3 as an adverse prognostic biomarker in hepatocellular carcinoma.Dig. Dis. Sci.20216641110112610.1007/s10620‑020‑06260‑z32333311
     [Google Scholar]
  118. NguyenC.T. WeisenbergerD.J. VelicescuM. GonzalesF.A. LinJ.C. LiangG. JonesP.A. Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine.Cancer Res.200262226456646112438235
     [Google Scholar]
  119. ChenH. ZhangT. ShengY. ZhangC. PengY. WangX. ZhangC. Methylation profiling of multiple tumor suppressor genes in hepatocellular carcinoma and the epigenetic mechanism of 3OST2 regulation.J. Cancer20156874074910.7150/jca.1169126185536
     [Google Scholar]
  120. MagerlC. EllingerJ. BraunschweigT. KremmerE. KochL.K. HöllerT. BüttnerR. LüscherB. GütgemannI. H3K4 dimethylation in hepatocellular carcinoma is rare compared with other hepatobiliary and gastrointestinal carcinomas and correlates with expression of the methylase Ash2 and the demethylase LSD1.Hum. Pathol.201041218118910.1016/j.humpath.2009.08.00719896696
     [Google Scholar]
  121. ShonJ.K. ShonB.H. ParkI.Y. LeeS.U. FaL. ChangK.Y. ShinJ.H. LeeY.I. Hepatitis B virus-X protein recruits histone deacetylase 1 to repress insulin-like growth factor binding protein 3 transcription.Virus Res.20091391142110.1016/j.virusres.2008.09.00618948152
     [Google Scholar]
  122. HeC. XuJ. ZhangJ. XieD. YeH. XiaoZ. CaiM. XuK. ZengY. LiH. WangJ. High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma.Hum. Pathol.20124391425143510.1016/j.humpath.2011.11.00322406368
     [Google Scholar]
  123. WongC.M. WeiL. LawC.T. HoD.W.H. TsangF.H.C. AuS.L.K. SzeK.M.F. LeeJ.M.F. WongC.C.L. NgI.O.L. Up‐regulation of histone methyltransferase SETDB1 by multiple mechanisms in hepatocellular carcinoma promotes cancer metastasis.Hepatology201663247448710.1002/hep.2830426481868
     [Google Scholar]
  124. ZhangX. WuJ. ChoiniereJ. YangZ. HuangY. BennettJ. WangL. Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a.Toxicol. Appl. Pharmacol.2016304424710.1016/j.taap.2016.05.01527217333
     [Google Scholar]
  125. RikimaruT. TaketomiA. YamashitaY. ShirabeK. HamatsuT. ShimadaM. MaeharaY. Clinical significance of histone deacetylase 1 expression in patients with hepatocellular carcinoma.Oncology2007721-2697410.1159/00011110618004079
     [Google Scholar]
  126. DuongF.H. ChristenV. LinS. HeimM.H. Hepatitis C virus-induced up-regulation of protein phosphatase 2A inhibits histone modification and DNA damage repair.Hepatology201051374175120043320
     [Google Scholar]
  127. LiuY.X. LiQ.Z. CaoY.N. ZhangL.Q. Identification of key genes and important histone modifications in hepatocellular carcinoma.Comput. Struct. Biotechnol. J.2020182657266910.1016/j.csbj.2020.09.01333033585
     [Google Scholar]
  128. XuY. LiaoW. LuoQ. YangD. PanM. Histone acetylation regulator-mediated acetylation patterns define tumor malignant pathways and tumor microenvironment in hepatocellular carcinoma.Front. Immunol.20221376104610.3389/fimmu.2022.76104635145517
     [Google Scholar]
  129. GuichardC. AmaddeoG. ImbeaudS. LadeiroY. PelletierL. MaadI.B. CalderaroJ. Bioulac-SageP. LetexierM. DegosF. ClémentB. BalabaudC. ChevetE. LaurentA. CouchyG. LetouzéE. CalvoF. Zucman-RossiJ. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.Nat. Genet.201244669469810.1038/ng.225622561517
     [Google Scholar]
  130. WilsonB.G. RobertsC.W.M. SWI/SNF nucleosome remodellers and cancer.Nat. Rev. Cancer201111748149210.1038/nrc306821654818
     [Google Scholar]
  131. LiM. ZhaoH. ZhangX. WoodL.D. AndersR.A. ChotiM.A. PawlikT.M. DanielH.D. KannangaiR. OfferhausG.J.A. VelculescuV.E. WangL. ZhouS. VogelsteinB. HrubanR.H. PapadopoulosN. CaiJ. TorbensonM.S. KinzlerK.W. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma.Nat. Genet.201143982882910.1038/ng.90321822264
     [Google Scholar]
  132. HuB. LinJ.Z. YangX.B. SangX.T. The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review.Cell Prolif.2020534e1279110.1111/cpr.1279132162380
     [Google Scholar]
  133. ZhouY. XuQ. TaoL. ChenY. ShuY. WuZ. LuC. ShiY. BuH. Enhanced SMARCD1, a subunit of the SWI/SNF complex, promotes liver cancer growth through the mTOR pathway.Clin. Sci.2020134121457147210.1042/CS2020024432514535
     [Google Scholar]
  134. CalinG.A. CroceC.M. MicroRNA signatures in human cancers.Nat. Rev. Cancer200661185786610.1038/nrc199717060945
     [Google Scholar]
  135. WangW. ZhaoL.J. TanY.X. RenH. QiZ.T. MiR-138 induces cell cycle arrest by targeting cyclin D3 in hepatocellular carcinoma.Carcinogenesis20123351113112010.1093/carcin/bgs11322362728
     [Google Scholar]
  136. JiJ. ShiJ. BudhuA. YuZ. ForguesM. RoesslerS. AmbsS. ChenY. MeltzerP.S. CroceC.M. QinL.X. ManK. LoC.M. LeeJ. NgI.O.L. FanJ. TangZ.Y. SunH.C. WangX.W. MicroRNA expression, survival, and response to interferon in liver cancer.N. Engl. J. Med.2009361151437144710.1056/NEJMoa090128219812400
     [Google Scholar]
  137. LiangL. WongC.M. YingQ. FanD.N.Y. HuangS. DingJ. YaoJ. YanM. LiJ. YaoM. NgI.O.L. HeX. MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2.Hepatology20105251731174010.1002/hep.2390420827722
     [Google Scholar]
  138. YangH. FangF. ChangR. YangL. MicroRNA-140-5p suppresses tumor growth and metastasis by targeting transforming growth factor β receptor 1 and fibroblast growth factor 9 in hepatocellular carcinoma.Hepatology201358120521710.1002/hep.2631523401231
     [Google Scholar]
  139. JühlingF. HamdaneN. CrouchetE. LiS. El SaghireH. MukherjiA. FujiwaraN. OudotM.A. ThumannC. SavianoA. Roca SuarezA.A. GotoK. MasiaR. SojoodiM. AroraG. AikataH. OnoA. TabrizianP. SchwartzM. PolyakS.J. DavidsonI. SchmidlC. BockC. SchusterC. ChayamaK. PessauxP. TanabeK.K. HoshidaY. ZeiselM.B. DuongF.H.T. FuchsB.C. BaumertT.F. Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma.Gut202170115716910.1136/gutjnl‑2019‑31891832217639
     [Google Scholar]
  140. GailhousteL. LiewL.C. YasukawaK. HatadaI. TanakaY. NakagamaH. OchiyaT. Differentiation therapy by epigenetic reconditioning exerts antitumor effects on liver cancer cells.Mol. Ther.20182671840185410.1016/j.ymthe.2018.04.01829759938
     [Google Scholar]
  141. MeiQ. ChenM. LuX. LiX. DuanF. WangM. LuoG. HanW. An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma.Oncotarget2015618166981671110.18632/oncotarget.367725895027
     [Google Scholar]
  142. JansenY.J.L. VersetG. SchatsK. Van DamP.J. SeremetT. KockxM. Van LaethemJ.L.B. NeynsB. Phase I clinical trial of decitabine (5-aza-2′-deoxycytidine) administered by hepatic arterial infusion in patients with unresectable liver-predominant metastases.ESMO Open201942e00046410.1136/esmoopen‑2018‑00046430962963
     [Google Scholar]
  143. LiuM. ZhangL. LiH. HinoueT. ZhouW. OhtaniH. El-KhoueiryA. DanielsJ. O’ConnellC. DorffT.B. LuQ. WeisenbergerD.J. LiangG. Integrative epigenetic analysis reveals therapeutic targets to the DNA methyltransferase inhibitor guadecitabine (SGI‐110) in hepatocellular carcinoma.Hepatology20186841412142810.1002/hep.3009129774579
     [Google Scholar]
  144. TakW.Y. RyooB.Y. LimH.Y. KimD.Y. OkusakaT. IkedaM. HidakaH. YeonJ.E. MizukoshiE. MorimotoM. LeeM.A. YasuiK. KawaguchiY. HeoJ. MoritaS. KimT.Y. FuruseJ. KatayamaK. AramakiT. HaraR. KimuraT. NakamuraO. KudoM. Phase I/II study of first-line combination therapy with sorafenib plus resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced hepatocellular carcinoma in east Asian patients.Invest. New Drugs20183661072108410.1007/s10637‑018‑0658‑x30198057
     [Google Scholar]
  145. BitzerM. HorgerM. GianniniE.G. GantenT.M. WörnsM.A. SivekeJ.T. DollingerM.M. GerkenG. ScheulenM.E. WegeH. ZagonelV. CilloU. TrevisaniF. SantoroA. MontesarchioV. MalekN.P. HolzapfelJ. HerzT. AmmendolaA.S. PegoraroS. HaunsB. MaisA. LauerU.M. HenningS.W. HentschB. Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma : The SHELTER study.J. Hepatol.201665228028810.1016/j.jhep.2016.02.04326952006
     [Google Scholar]
  146. ChangY. LeeY.B. ChoE.J. LeeJ.H. YuS.J. KimY.J. YoonJ.H. CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.BMC Cancer2020201100110.1186/s12885‑020‑07471‑333059615
     [Google Scholar]
  147. JungD.E. ParkS.B. KimK. KimC. SongS.Y. CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway.Sci. Rep.2017711092110.1038/s41598‑017‑11094‑328883618
     [Google Scholar]
  148. YinY. ZhangM. DorfmanR.G. LiY. ZhaoZ. PanY. ZhouQ. HuangS. ZhaoS. YaoY. ZouX. Histone deacetylase 3 overexpression in human cholangiocarcinoma and promotion of cell growth via apoptosis inhibition.Cell Death Dis.201786e285610.1038/cddis.2016.45728569784
     [Google Scholar]
  149. LlopizD. RuizM. VillanuevaL. IglesiasT. SilvaL. EgeaJ. LasarteJ.J. PivetteP. Trochon-JosephV. VasseurB. DixonG. SangroB. SarobeP. Enhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma model.Cancer Immunol. Immunother.201968337939310.1007/s00262‑018‑2283‑030547218
     [Google Scholar]
  150. YeoW. ChungH.C. ChanS.L. WangL.Z. LimR. PicusJ. BoyerM. MoF.K.F. KohJ. RhaS.Y. HuiE.P. JeungH.C. RohJ.K. YuS.C.H. ToK.F. TaoQ. MaB.B. ChanA.W.H. TongJ.H.M. ErlichmanC. ChanA.T.C. GohB.C. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: A multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group.J. Clin. Oncol.201230273361336710.1200/JCO.2011.41.239522915658
     [Google Scholar]
  151. NakatsukaT. TateishiK. KatoH. FujiwaraH. YamamotoK. KudoY. NakagawaH. TanakaY. IjichiH. IkenoueT. IshizawaT. HasegawaK. TachibanaM. ShinkaiY. KoikeK. Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis.Cell Death Dis.20211219910.1038/s41419‑020‑03381‑133468997
     [Google Scholar]
  152. Bárcena-VarelaM. CarusoS. LlerenaS. Álvarez-SolaG. UriarteI. LatasaM.U. UrtasunR. RebouissouS. AlvarezL. JimenezM. SantamaríaE. Rodriguez-OrtigosaC. MazzaG. RomboutsK. San José-EnerizE. RabalO. AgirreX. IraburuM. Santos-LasoA. BanalesJ.M. Zucman-RossiJ. PrósperF. OyarzabalJ. BerasainC. ÁvilaM.A. Fernández-BarrenaM.G. Dual targeting of histone methyltransferase G9a and DNA‐methyltransferase 1 for the treatment of experimental hepatocellular carcinoma.Hepatology201969258760310.1002/hep.3016830014490
     [Google Scholar]
  153. WangR. JinY. YaoX.H. FanW. ZhangJ. CaoY. LiJ. A novel mechanism of the M1‐M2 methionine adenosyltransferase switch‐mediated hepatocellular carcinoma metastasis.Mol. Carcinog.20185791201121210.1002/mc.2283629749642
     [Google Scholar]
  154. PascaleR.M. PeittaG. SimileM.M. FeoF. Alterations of methionine metabolism as potential targets for the prevention and therapy of hepatocellular carcinoma.Medicina201955629610.3390/medicina5506029631234428
     [Google Scholar]
  155. HungM.H. LeeJ.S. MaC. DiggsL.P. HeinrichS. ChangC.W. MaL. ForguesM. BudhuA. ChaisaingmongkolJ. RuchirawatM. RuppinE. GretenT.F. WangX.W. Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma.Nat. Commun.2021121145510.1038/s41467‑021‑21804‑133674593
     [Google Scholar]
  156. ZhaoQ. ZhangZ. LiJ. XuF. ZhangB. LiuM. LiuY. ChenH. YangJ. ZhangJ. Lysine acetylome study of human hepatocellular carcinoma tissues for biomarkers and therapeutic targets discovery.Front. Genet.20201157266310.3389/fgene.2020.57266333093847
     [Google Scholar]
  157. FerlayJ. ColombetM. SoerjomataramI. ParkinD.M. PiñerosM. ZnaorA. BrayF. Cancer statistics for the year 2020: An overview.Int. J. Cancer2021149477878910.1002/ijc.3358833818764
     [Google Scholar]
  158. KarimiP. IslamiF. AnandasabapathyS. FreedmanN.D. KamangarF. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention.Cancer Epidemiol. Biomarkers Prev.201423570071310.1158/1055‑9965.EPI‑13‑105724618998
     [Google Scholar]
  159. MachlowskaJ. BajJ. SitarzM. MaciejewskiR. SitarzR. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies.Int. J. Mol. Sci.20202111401210.3390/ijms2111401232512697
     [Google Scholar]
  160. LaurénP. The two histological main types of gastric carcinoma: diffuse and so‐called intestinal‐type carcinoma: An attempt at a histo‐clinical classification.Acta Pathol. Microbiol. Scand.1965641314910.1111/apm.1965.64.1.3114320675
     [Google Scholar]
  161. AbdelfatahE. KernerZ. NandaN. AhujaN. Epigenetic therapy in gastrointestinal cancer: The right combination.Therap. Adv. Gastroenterol.20169456057910.1177/1756283X1664424727366224
     [Google Scholar]
  162. EbrahimiV. SoleimanianA. EbrahimiT. AzargunR. YazdaniP. EyvaziS. TarhrizV. Epigenetic modifications in gastric cancer: Focus on DNA methylation.Gene202074214457710.1016/j.gene.2020.14457732171825
     [Google Scholar]
  163. QiuY.S. LiaoG.J. JiangN.N. DNA methylation-mediated silencing of regenerating protein 1 Alpha (REG1A) Affects Gastric Cancer Prognosis.Med. Sci. Monit.2017235834584310.12659/MSM.90470629222406
     [Google Scholar]
  164. GómezA. PatoM.L. BujandaL. SalaN. CompanioniO. CosmeÁ. TufanoM. HanlyD.J. GarcíaN. Sanz-AnquelaJ.M. GisbertJ.P. LópezC. ElizaldeJ.I. CuatrecasasM. AndreuV. PaulesM.J. Martín-ArranzM.D. OrtegaL. PovesE. BarrioJ. TorresM.Á. MuñozG. FerrándezÁ. Ramírez-LázaroM.J. LarioS. GonzálezC.A. EstellerM. BerdascoM. Follow-up study confirms the presence of gastric cancer DNA methylation hallmarks in high-risk precursor lesions.Cancers20211311276010.3390/cancers1311276034199386
     [Google Scholar]
  165. VahidiS. MirzajaniE. NorollahiS.E. AziminezhadM. SamadaniA.A. Performance of DNA methylation on the molecular pathogenesis of Helicobacter pylori in gastric cancer; targeted therapy approach.J. Pharmacopuncture20222528810010.3831/KPI.2022.25.2.8835837145
     [Google Scholar]
  166. FattahiS. Kosari-MonfaredM. GhadamiE. GolpourM. KhodadadiP. GhasemiyanM. Akhavan-NiakiH. Infection‐associated epigenetic alterations in gastric cancer: New insight in cancer therapy.J. Cell. Physiol.2018233129261927010.1002/jcp.2703030076708
     [Google Scholar]
  167. LiC. ZhengY. PuK. ZhaoD. WangY. GuanQ. ZhouY. A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer.Cancer Cell Int.20202018810.1186/s12935‑020‑1156‑832206039
     [Google Scholar]
  168. ShimuraT. KandimallaR. OkugawaY. OhiM. ToiyamaY. HeC. GoelA. Novel evidence for m6A methylation regulators as prognostic biomarkers and FTO as a potential therapeutic target in gastric cancer.Br. J. Cancer2022126222823710.1038/s41416‑021‑01581‑w34675398
     [Google Scholar]
  169. WangQ. ChenC. DingQ. ZhaoY. WangZ. ChenJ. JiangZ. ZhangY. XuG. ZhangJ. ZhouJ. SunB. ZouX. WangS. METTL3-mediated m 6 A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance.Gut20206971193120510.1136/gutjnl‑2019‑31963931582403
     [Google Scholar]
  170. ReyesM.E. PulgarV. VivalloC. IliC.G. Mora-LagosB. BrebiP. Epigenetic modulation of cytokine expression in gastric cancer: influence on angiogenesis, metastasis and chemoresistance.Front. Immunol.202415134753010.3389/fimmu.2024.134753038455038
     [Google Scholar]
  171. ZhangX. YashiroM. OhiraM. RenJ. HirakawaK. Synergic antiproliferative effect of DNA methyltransferase inhibitor in combination with anticancer drugs in gastric carcinoma.Cancer Sci.200697993894410.1111/j.1349‑7006.2006.00253.x16805821
     [Google Scholar]
  172. KangS.H. BangY.J. ImY.H. YangH.K. LeeD.A. LeeH.Y. LeeH.S. KimN.K. KimS.J. Transcriptional repression of the transforming growth factor-β type I receptor gene by DNA methylation results in the development of TGF-β resistance in human gastric cancer.Oncogene199918517280728610.1038/sj.onc.120314610602482
     [Google Scholar]
  173. TangS.Y. ZhouP.J. MengY. ZengF.R. DengG.T. Gastric cancer: An epigenetic view.World J. Gastrointest. Oncol.20221419010910.4251/wjgo.v14.i1.9035116105
     [Google Scholar]
  174. YamadaL. SaitoM. Thar MinA.K. SaitoK. AshizawaM. KaseK. NakajimaS. OnozawaH. OkayamaH. EndoH. FujitaS. SakamotoW. SazeZ. MommaT. MimuraK. OhkiS. KonoK. Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer.Gastric Cancer2021241607110.1007/s10120‑020‑01094‑032506298
     [Google Scholar]
  175. ZhangX.H. KangH.Q. TaoY.Y. LiY.H. ZhaoJ.R. Ya-Gao MaL.Y. LiuH.M. Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity.Eur. J. Med. Chem.202121811339210.1016/j.ejmech.2021.11339233831778
     [Google Scholar]
  176. XiongK. ZhangH. DuY. TianJ. DingS. Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer.Exp. Mol. Med.201951811510.1038/s12276‑019‑0301‑831451695
     [Google Scholar]
  177. CalcagnoD.Q. WisnieskiF. MotaE.R.S. Maia de SousaS.B. Costa da SilvaJ.M. LealM.F. GigekC.O. SantosL.C. RasmussenL.T. AssumpçãoP.P. BurbanoR.R. SmithM.A.C. Role of histone acetylation in gastric cancer: Implications of dietetic compounds and clinical perspectives.Epigenomics201911334936210.2217/epi‑2018‑008130672330
     [Google Scholar]
  178. JieM. WuY. GaoM. LiX. LiuC. OuyangQ. TangQ. ShanC. LvY. ZhangK. DaiQ. ChenY. ZengS. LiC. WangL. HeF. HuC. YangS. CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification.Mol. Cancer20201915610.1186/s12943‑020‑01160‑232164722
     [Google Scholar]
  179. YueY. LinX. QiuX. YangL. WangR. The molecular roles and clinical implications of non-coding RNAs in gastric cancer.Front. Cell Dev. Biol.2021980274510.3389/fcell.2021.80274534966746
     [Google Scholar]
  180. LiuA. YanZ. JiangL. LvZ. LiY. WangB. The role of non-coding RNA in the diagnosis and treatment of Helicobacter pylori-related gastric cancer, with a focus on inflammation and immune response.Front. Med.20229100902110.3389/fmed.2022.100902136314013
     [Google Scholar]
  181. LiB. HeL. LiuH. Down-regulation of LINC00341 predicts a poor prognosis and acts as a tumor suppressor in gastric cancer.Int. J. Clin. Exp. Pathol.20181184205421231949815
     [Google Scholar]
  182. XuJ.L. YuanL. TangY.C. XuZ.Y. XuH.D. ChengX.D. QinJ.J. The role of autophagy in gastric cancer chemoresistance: friend or foe?Front. Cell Dev. Biol.2020862142810.3389/fcell.2020.62142833344463
     [Google Scholar]
  183. SunZ. HeZ. LiuR. ZhangZ. Cation lipid-assisted PEG6-PLGA polymer nanoparticles encapsulated knocking down long ncRNAs reverse non-coding RNA of xist through the support vector machine model to regulate the molecular mechanisms of gastric cancer cell apoptosis.J. Biomed. Nanotechnol.20211771305131910.1166/jbn.2021.310734446134
     [Google Scholar]
  184. YangQ. ChenY. GuoR. DaiY. TangL. ZhaoY. WuX. LiM. DuF. ShenJ. YiT. XiaoZ. WenQ. Interaction of ncRNA and epigenetic modifications in gastric cancer: focus on histone modification.Front. Oncol.20221182274510.3389/fonc.2021.82274535155211
     [Google Scholar]
  185. RahibL. SmithB.D. AizenbergR. RosenzweigA.B. FleshmanJ.M. MatrisianL.M. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States.Cancer Res.201474112913292110.1158/0008‑5472.CAN‑14‑015524840647
     [Google Scholar]
  186. KleinA.P. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors.Nat. Rev. Gastroenterol. Hepatol.202118749350210.1038/s41575‑021‑00457‑x34002083
     [Google Scholar]
  187. FerroneC.R. Pieretti-VanmarckeR. BloomJ.P. ZhengH. SzymonifkaJ. WargoJ.A. ThayerS.P. LauwersG.Y. DeshpandeV. Mino-KenudsonM. Fernández-del CastilloC. LillemoeK.D. WarshawA.L. Pancreatic ductal adenocarcinoma: Long-term survival does not equal cure.Surgery20121523Suppl. 1S43S4910.1016/j.surg.2012.05.02022763261
     [Google Scholar]
  188. VersemannL. HessmannE. UlisseM. Epigenetic therapeutic strategies to target molecular and cellular heterogeneity in pancreatic cancer.Visc. Med.2022381111910.1159/00051985935291698
     [Google Scholar]
  189. WangS.S. XuJ. JiK.Y. HwangC.I. Epigenetic alterations in pancreatic cancer metastasis.Biomolecules2021118108210.3390/biom1108108234439749
     [Google Scholar]
  190. EmbuscadoE.E. LaheruD. RicciF. YunK.J. de Boom WitzelS. SeigelA. FlickingerK. HidalgoM. BovaG.S. Iacobuzio-DonahueC.A. Immortalizing the complexity of cancer metastasis: Genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy.Cancer Biol. Ther.20054554855410.4161/cbt.4.5.166315846069
     [Google Scholar]
  191. ChenG. LongJ. ZhuR. YangG. QiuJ. ZhaoF. LiuY. TaoJ. ZhangT. ZhaoY. Identification and validation of constructing the prognostic model with four DNA methylation-driven genes in pancreatic cancer.Front. Cell Dev. Biol.2022970966910.3389/fcell.2021.70966935087823
     [Google Scholar]
  192. XiaoM. LiangX. YanZ. ChenJ. ZhuY. XieY. LiY. LiX. GaoQ. FengF. FuG. GaoY. A DNA-methylation-driven genes based prognostic signature reveals immune microenvironment in pancreatic cancer.Front. Immunol.20221380396210.3389/fimmu.2022.80396235222383
     [Google Scholar]
  193. SanaeiM. KavoosiF. HosseiniF. Effect of zebularine on p16INK4a, p14ARF, p15INK4b, and DNA Methyltransferase 1 gene expression, cell growth inhibition, and apoptosis induction in human hepatocellular carcinoma PLC/PRF5 and pancreatic cancer PA-TU-8902 cell lines.Iran. J. Pharm. Res.202019419320233841535
     [Google Scholar]
  194. SanaeiM. KavoosiF. MohammadiM. KhanezadM. Effect of 5-aza-2′-deoxycytidine on p16INK4a, p14ARF, p15INK4b genes expression, cell viability, and apoptosis in PLC/PRF5 and MIA Paca-2 cell lines.Iran. J. Ped. Hematol. Oncol.201910.18502/ijpho.v9i4.1570
     [Google Scholar]
  195. CaoF. WeiA. HuX. HeY. ZhangJ. XiaL. TuK. YuanJ. GuoZ. LiuH. XieD. LiA. Integrated epigenetic biomarkers in circulating cell-free DNA as a robust classifier for pancreatic cancer.Clin. Epigenetics202012111210.1186/s13148‑020‑00898‑232703318
     [Google Scholar]
  196. GulerG.D. NingY. KuC.J. PhillipsT. McCarthyE. EllisonC.K. BergamaschiA. CollinF. LloydP. ScottA. AntoineM. WangW. ChauK. AshworthA. QuakeS.R. LevyS. Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA.Nat. Commun.2020111527010.1038/s41467‑020‑18965‑w33077732
     [Google Scholar]
  197. ManoochehriM. WuY. GieseN.A. StrobelO. KutschmannS. HallerF. HoheiselJ.D. MoskalevE.A. HackertT. BauerA.S. SST gene hypermethylation acts as a pan‐cancer marker for pancreatic ductal adenocarcinoma and multiple other tumors: Toward its use for blood‐based diagnosis.Mol. Oncol.20201461252126710.1002/1878‑0261.1268432243066
     [Google Scholar]
  198. XuY. ZhuQ. Histone modifications represent a key epigenetic feature of epithelial-to-mesenchyme transition in pancreatic cancer.Int. J. Mol. Sci.2023245482010.3390/ijms2405482036902253
     [Google Scholar]
  199. WangH.C. ShihH.Y. WuC.C. ChenL.T. LuoC.W. LiuY.C. DuJ.S. HuangM.C. SuY.Y. ChenH.D. HsiaoH.H. MoiS.H. PanM.R. Clustering of chromatin remodeling enzymes predicts prognosis and clinical benefit of therapeutic strategy in pancreatic cancer.Int. J. Med. Sci.202219101615162710.7150/ijms.7380036185333
     [Google Scholar]
  200. BlaauboerA. van KoetsveldP.M. MustafaD.A.M. DumasJ. DoganF. van ZwienenS. van EijckC.H.J. HoflandL.J. The Class I HDAC inhibitor valproic acid strongly potentiates gemcitabine efficacy in pancreatic cancer by immune system activation.Biomedicines202210351710.3390/biomedicines1003051735327319
     [Google Scholar]
  201. BaudenM. KristlT. SasorA. AnderssonB. Marko-VargaG. AnderssonR. AnsariD. Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma.BMC Cancer201717181010.1186/s12885‑017‑3834‑z29197353
     [Google Scholar]
  202. KoustasE. TrifylliE.M. SarantisP. PapadopoulosN. PapanikolopoulosK. AloizosG. DamaskosC. GarmpisN. GarmpiA. KaramouzisM.V. The Emerging Role of MicroRNAs and autophagy mechanism in pancreatic cancer progression: Future therapeutic approaches.Genes20221310186810.3390/genes1310186836292753
     [Google Scholar]
  203. VieiraN.F. SerafiniL.N. NovaisP.C. NetoF.S.L. CirinoM.L.A. KempR. ArdenghJ.C. SaggioroF.P. GasparA.F. SankarankuttyA.K. JúniorJ.R.L. TirapelliD.P.C. dos SantosJ.S. The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis.Oncotarget202112171638165010.18632/oncotarget.2803834434493
     [Google Scholar]
  204. AshrafizadehM. RabieeN. KumarA.P. SethiG. ZarrabiA. WangY. Long noncoding RNAs (lncRNAs) in pancreatic cancer progression.Drug Discov. Today20222782181219810.1016/j.drudis.2022.05.01235589014
     [Google Scholar]
  205. TangX. ZhangM. SunL. XuF. PengX. ZhangY. DengY. WuS. The biological function delineated across pan-cancer levels through lncRNA-based prognostic risk assessment factors for pancreatic cancer.Front. Cell Dev. Biol.2021969465210.3389/fcell.2021.69465234195204
     [Google Scholar]
  206. AierI. SemwalR. SharmaA. VaradwajP.K. A systematic assessment of statistics, risk factors, and underlying features involved in pancreatic cancer.Cancer Epidemiol.20195810411010.1016/j.canep.2018.12.00130537645
     [Google Scholar]
  207. CoyleKM BoudreauJE MarcatoP Genetic mutations and epigenetic modifications: Driving cancer and informing precision medicine.Biomed Res Int20172017962087010.1155/2017/9620870
     [Google Scholar]
  208. ArmaghanyT. WilsonJ.D. ChuQ. MillsG. Genetic alterations in colorectal cancer.Gastrointest. Cancer Res.201251192722574233
     [Google Scholar]
  209. BaeJ.M. KimJ.H. KwakY. LeeD.W. ChaY. WenX. LeeT.H. ChoN.Y. JeongS.Y. ParkK.J. HanS.W. LeeH.S. KimT.Y. KangG.H. Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.Br. J. Cancer201711681012102010.1038/bjc.2017.5228278514
     [Google Scholar]
  210. HermanJ.G. UmarA. PolyakK. GraffJ.R. AhujaN. IssaJ.P.J. MarkowitzS. WillsonJ.K.V. HamiltonS.R. KinzlerK.W. KaneM.F. KolodnerR.D. VogelsteinB. KunkelT.A. BaylinS.B. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma.Proc. Natl. Acad. Sci.199895126870687510.1073/pnas.95.12.68709618505
     [Google Scholar]
  211. SuterC.M. MartinD.I. WardR.L. Hypomethylation of L1 retrotransposons in colorectal cancer and adjacent normal tissue.Int. J. Colorectal Dis.20041929510110.1007/s00384‑003‑0539‑314534800
     [Google Scholar]
  212. ZhouX. WangL. XiaoJ. SunJ. YuL. ZhangH. MengX. YuanS. TimofeevaM. LawP.J. HoulstonR.S. DingK. DunlopM.G. TheodoratouE. LiX. Alcohol consumption, DNA methylation and colorectal cancer risk: Results from pooled cohort studies and Mendelian randomization analysis.Int. J. Cancer20221511839410.1002/ijc.3394535102554
     [Google Scholar]
  213. LiD. ZhangL. FuJ. HuangH. SunS. ZhangD. ZhaoL. Ucheojor OnwukaJ. ZhaoY. CuiB. SCTR hypermethylation is a diagnostic biomarker in colorectal cancer.Cancer Sci.2020111124558456610.1111/cas.1466132970347
     [Google Scholar]
  214. YinH. HuangZ. NiuS. MingL. JiangH. GuL. HuangW. XieJ. HeY. ZhangC. 5-Methylcytosine (m5C) modification in peripheral blood immune cells is a novel non-invasive biomarker for colorectal cancer diagnosis.Front. Immunol.20221396792110.3389/fimmu.2022.96792136211353
     [Google Scholar]
  215. ZhangX. HuoX. GuoH. XueL. Combined inhibition of PARP and EZH2 for cancer treatment: Current status, opportunities, and challenges.Front. Pharmacol.20221396524410.3389/fphar.2022.96524436263120
     [Google Scholar]
  216. WangH.L. ChenY. WangY.Q. TaoE.W. TanJ. LiuQ.Q. LiC.M. TongX.M. GaoQ.Y. HongJ. ChenY.X. FangJ.Y. Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability.Nat. Commun.2022131612110.1038/s41467‑022‑33903‑836253417
     [Google Scholar]
  217. ChenX. WongP. RadanyE. WongJ.Y.C. HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells.Cancer Biother. Radiopharm.200924668969910.1089/cbr.2009.062920025549
     [Google Scholar]
  218. MurphyA.G. WalkerR. LutzE.R. ParkinsonR. AhujaN. ZhengL. Epigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer.J. Clin. Oncol.201937459210.1200/JCO.2019.37.4_suppl.591
     [Google Scholar]
  219. YangL. ZhangX. HuG. Circulating non-coding RNAs as new biomarkers and novel therapeutic targets in colorectal cancer.Clin. Transl. Oncol.202123112220223610.1007/s12094‑021‑02639‑034275108
     [Google Scholar]
  220. ChenX. JiaM. JiJ. ZhaoZ. ZhaoY. Exosome-derived non-coding RNAs in the tumor microenvironment of colorectal cancer: Possible functions, mechanisms and clinical applications.Front. Oncol.20221288753210.3389/fonc.2022.88753235646623
     [Google Scholar]
  221. ZhangW. JiangZ. TangD. The value of exosome-derived noncoding RNAs in colorectal cancer proliferation, metastasis, and clinical applications.Clin. Transl. Oncol.202224122305231810.1007/s12094‑022‑02908‑635921060
     [Google Scholar]
  222. StrubbergA.M. MadisonB.B. MicroRNAs in the etiology of colorectal cancer: Pathways and clinical implications.Dis. Model. Mech.201710319721410.1242/dmm.02744128250048
     [Google Scholar]
  223. ShigeyasuK. TodenS. OzawaT. MatsuyamaT. NagasakaT. IshikawaT. SahooD. GhoshP. UetakeH. FujiwaraT. GoelA. The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer.Mol. Cancer202019115510.1186/s12943‑020‑01277‑433148262
     [Google Scholar]
  224. LorinczA.T. The promise and the problems of epigenetic biomarkers in cancer.Expert Opin. Med. Diagn.20115537537910.1517/17530059.2011.59012922003365
     [Google Scholar]
  225. RenL. YangY. LiW. YangH. ZhangY. GeB. ZhangS. DuG. WangJ. Recent advances in epigenetic anticancer therapeutics and future perspectives.Front. Genet.202313108539110.3389/fgene.2022.108539136685834
     [Google Scholar]
  226. TinariN. De TursiM. GrassadoniaA. ZilliM. StuppiaL. IacobelliS. NatoliC. An epigenetic approach to pancreatic cancer treatment: the prospective role of histone deacetylase inhibitors.Curr. Cancer Drug Targets201212443945210.2174/15680091280019088422309455
     [Google Scholar]
  227. ReeA.H. DuelandS. FolkvordS. HoleK.H. SeierstadT. JohansenM. AbrahamsenT.W. FlatmarkK. Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: The Pelvic Radiation and Vorinostat (PRAVO) phase 1 study.Lancet Oncol.201011545946410.1016/S1470‑2045(10)70058‑920378407
     [Google Scholar]
  228. GravinaG.L. FestucciaC. MaramponF. PopovV.M. PestellR.G. ZaniB.M. TomboliniV. Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation.Mol. Cancer20109130510.1186/1476‑4598‑9‑30521108789
     [Google Scholar]
  229. PiliR. LiuG. ChintalaS. VerheulH. RehmanS. AttwoodK. LodgeM.A. WahlR. MartinJ.I. MilesK.M. PaesanteS. AdelaiyeR. GodoyA. KingS. ZwiebelJ. CarducciM.A. Combination of the histone deacetylase inhibitor vorinostat with bevacizumab in patients with clear-cell renal cell carcinoma: A multicentre, single-arm phase I/II clinical trial.Br. J. Cancer2017116787488310.1038/bjc.2017.3328222071
     [Google Scholar]
  230. Medina LópezR.A. Rivero BelenchonI. Mazuecos-QuirósJ. Congregado-RuízC.B. CouñagoF. Update on the treatment of metastatic renal cell carcinoma.World J. Clin. Oncol.20221311810.5306/wjco.v13.i1.135116228
     [Google Scholar]
  231. SchillerJT LowyDR An introduction to virus infections and human cancer.Recent Results Cancer Res202121711110.1007/978‑3‑030‑57362‑1_1
     [Google Scholar]
  232. MillerK.D. Fidler-BenaoudiaM. KeeganT.H. HippH.S. JemalA. SiegelR.L. Cancer statistics for adolescents and young adults, 2020.CA Cancer J. Clin.202070644345910.3322/caac.2163732940362
     [Google Scholar]
/content/journals/ccdt/10.2174/0115680096306639240520053736
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The Role of Epigenetic Mechanisms in the Treatment of GI Cancers
Curr. Cancer Drug Targets< 25, 923 (2025); https://doi.org/10.2174/0115680096306639240520053736
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  • Article Type:     Review Article
Keyword(s): DNA; DNA methylation; Epigenetic; gastrointestinal cancer; histone acetylation; treatment

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