Epigenetics in Cancer Therapy

Oncology-Epigenetics Cancer


  • Dr. Abikesh Prasada Kumar Mahapatra School of Pharmacy, OPJS University, Churu, Rajasthan, India
  • Vinod S. Mule Department of Pharmacology, Bombay Institute of Pharmacy and Research, Dombivali, Maharashtra, India-421201.
  • Dr Avula Naveen Associate professor, Department of pharmacology and therapeutics, AIIMS Bilaspur.
  • Dr. Somenath Ghosh Assistant Professor, P. G. Department of Zoology, Rajendra College, Chapra 841301, Bihar




Epigenetics, histone modification, DNA methylation, malignant cells, genetic expression, prevalent cancer


Epigenetics regulates parts of the genetic information accessible to cellular machinery, thus contributing to cellular diversity. Disruption of epigenetic harmonisation can lead to dysregulation of signaling pathways and contribute to diseases like cancer. Epigenetic processes are crucial in coordinating the normal growth and preservation of gene activity unique to mammal tissues. Epigenetic studies in current cancer research are vital for early detection through biomarker identification, understanding tumor heterogeneity, predicting treatment responses, and uncovering resistance mechanisms. This knowledge informs targeted therapies, enhances personalized medicine, and improves overall outcomes in cancer patients. This review comprehensively explores epigenetic processes in healthy cells, emphasizing histone modification-lysine acetylation and DNA methylation. The intricate mechanisms governing genetic expression and their dysregulation in cancer progression are also reviewed. Examining prevalent cancer types, this review stresses the pivotal role of epigenetics in understanding and potentially targeting these processes for therapeutic interventions.


Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004 May 27;429(6990):457-63.

Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nature reviews genetics. 2002 Jun 1;3(6):415-28.

Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010 Jan 1;31(1):27-36.

Hanahan D. Hallmarks of cancer: new dimensions. Cancer discovery. 2022 Jan 1;12(1):31-46.

Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, Han J, Wei X. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal transduction and targeted therapy. 2019 Dec 17;4(1):62.

Chakravarthi BV, Nepal S, Varambally S. Genomic and epigenomic alterations in cancer. The American journal of pathology. 2016 Jul 1;186(7):1724-35.

Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nature reviews genetics. 2002 Jun 1;3(6):415-28.

Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007 Feb 23;128(4):683-92.

Pa J. Cancer epigenetics comes of age. Nat Genet. 1999;21(2):163-7.

Jones PA, Martienssen R. A blueprint for a human epigenome project: the AACR human epigenome workshop.

Chakravarthi BV, Nepal S, Varambally S. Genomic and epigenomic alterations in cancer. The American journal of pathology. 2016 Jul 1;186(7):1724-35.

Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nature reviews Drug discovery. 2006 Jan 1;5(1):37-50.

Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature. 1997 Sep 18;389(6648):251-60.

Bure IV, Nemtsova MV, Kuznetsova EB. Histone modifications and non-coding RNAs: mutual epigenetic regulation and role in pathogenesis. International Journal of Molecular Sciences. 2022 May 22;23(10):5801.

Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007 Feb 23;128(4):683-92.

Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Developmental biology. 2007 Feb 1;302(1):1-2.

Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2014 Aug 1;1839(8):627-43.

Padmanabhan B, Mathur S, Manjula R, Tripathi S. Bromodomain and extra-terminal (BET) family proteins: New therapeutic targets in major diseases. Journal of biosciences. 2016 Jun;41:295-311.

Pérez-Salvia M, Esteller M. Bromodomain inhibitors and cancer therapy: From structures to applications. Epigenetics. 2017 May 4;12(5):323-39.

Chan CH, Fang C, Qiao Y, Yarilina A, Prinjha RK, Ivashkiv LB. BET bromodomain inhibition suppresses transcriptional responses to cytokine‐Jak‐STAT signaling in a gene‐specific manner in human monocytes. European journal of immunology. 2015 Jan;45(1):287-97.

Huang M, Zeng S, Zou Y, Shi M, Qiu Q, Xiao Y, Chen G, Yang X, Liang L, Xu H. The suppression of bromodomain and extra‐terminal domain inhibits vascular inflammation by blocking NF‐κB and MAPK activation. British journal of pharmacology. 2017 Jan;174(1):101-15.

Xu Y, Vakoc CR. Targeting cancer cells with BET bromodomain inhibitors. Cold Spring Harbor perspectives in medicine. 2017 Feb 17:a026674.

Alaskhar Alhamwe B, Khalaila R, Wolf J, von Bülow V, Harb H, Alhamdan F, Hii CS, Prescott SL, Ferrante A, Renz H, Garn H. Histone modifications and their role in epigenetics of atopy and allergic diseases. Allergy, Asthma & Clinical Immunology. 2018 Dec;14(1):1-6.

Di Ruscio A, Welner RS, Tenen DG, Amabile G. The second hit of DNA methylation. Molecular & cellular oncology. 2016 May 3;3(3):e1093690.

Doerfler W. DNA methylation—a regulatory signal in eukaryotic gene expression. Journal of General Virology. 1981 Nov;57(1):1-20.

Watt F, Molloy PL. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes & development. 1988 Sep 1;2(9):1136-43.

Balch C, Yan P, Craft T, Young S, Skalnik DG, Huang TH, Nephew KP. Antimitogenic and chemosensitizing effects of the methylation inhibitor zebularine in ovarian cancer. Molecular cancer therapeutics. 2005 Oct 1;4(10):1505-14.

Spitz F, Furlong EE. Transcription factors: from enhancer binding to developmental control. Nature reviews genetics. 2012 Sep;13(9):613-26.

Brown LJ, Achinger-Kawecka J, Portman N, Clark S, Stirzaker C, Lim E. Epigenetic Therapies and Biomarkers in Breast Cancer. Cancers. 2022; 14(3):474. https://doi.org/10.3390/cancers14030474

Liaw A, Liu C, Ivanovski S, Han P. The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review. Cells. 2022; 11(20):3211. https://doi.org/10.3390/cells11203211

Ilango S, Paital B, Jayachandran P, Padma PR, Nirmaladevi R. Epigenetic alterations in cancer. Frontiers in Bioscience-Landmark. 2020 Mar 1;25(6):1058-109.

Tan T, Shi P, Abbas MN, Wang Y, Xu J, Chen Y, Cui H. Epigenetic modification regulates tumor progression and metastasis through EMT. International Journal of Oncology. 2022 Jun 1;60(6):1-7.

Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA biology. 2012 Jun 1;9(6):703-19.

Ahuja N, Easwaran H, Baylin SB. Harnessing the potential of epigenetic therapy to target solid tumors. The Journal of clinical investigation. 2014 Jan 2;124(1):56-63.

Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004 May 27;429(6990):457-63.

Chen Q, Zhu XY, Li YY, Meng ZQ. Epigenetic regulation and cancer. Oncology reports. 2014 Feb 1;31(2):523-32.

Shen L, Kondo Y, Ahmed S, Boumber Y, Konishi K, Guo Y, Chen X, Vilaythong JN, Issa JP. Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel. Cancer research. 2007 Dec 1;67(23):11335-43.

Kazanets A, Shorstova T, Hilmi K, Marques M, Witcher M. Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2016 Apr 1;1865(2):275-88.

Bodey B, Bodey Jr B, Siegel SE. Mechanisms and markers of carcinogenesis and neoplastic progression. Expert Opinion on Biological Therapy. 2005 Oct 1;5(10):1317-32.

Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell stem cell. 2014 Mar 6;14(3):275-91.

Rastogi V, Puri N, Mishra S, Arora S, Kaur G, Yadav L. An insight to oral epithelial dysplasia. Int J Head Neck Surg. 2013;4(2):74-82.

MiNNa Jd RJ. gazdaR aF. Focus on lung cancer. Cancer Cell. 2002;1:49-52.

Polyak K. Molecular alterations in ductal carcinoma in situ of the breast. Current opinion in oncology. 2002 Jan 1;14(1):92-6.

Califano J, Van Der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, Corio R, Lee D, Greenberg B, Koch W, Sidransky D. Genetic progression model for head and neck cancer: implications for field cancerization. Cancer research. 1996 Jun 1;56(11):2488-92.

Abate-Shen C, Shen MM. Molecular genetics of prostate cancer. Genes & development. 2000 Oct 1;14(19):2410-34.

Huang S. Gene expression profiling, genetic networks, and cellular states: an integrating concept for tumorigenesis and drug discovery. Journal of molecular medicine. 1999 Jun;77(6):469-80.

Baak JP, Path FR, Hermsen MA, Meijer G, Schmidt J, Janssen EA. Genomics and proteomics in cancer. European journal of cancer. 2003 Jun 1;39(9):1199-215.

Padmanabhan N, Ushijima T, Tan P. How to stomach an epigenetic insult: the gastric cancer epigenome. Nature reviews Gastroenterology & hepatology. 2017 Aug;14(8):467-78.

Arai T, Esaki Y, Inoshita N, Sawabe M, Kasahara I, Kuroiwa K, Honma N, Takubo K. Pathologic characteristics of gastric cancer in the elderly: a retrospective study of 994 surgical patients. Gastric cancer. 2004 Sep;7:154-9.

Hanai A, Tsukuma H, Hiyama T, Fujimoto I. Survival of patients with stomach cancer: results from population-based cancer registries. InGastric cancer 1997 (pp. 22-30). Oxford Univ. Press, New York.

Tahara E, Yokozaki H, Yasui W. Growth factors in gastric cancer. Gastric cancer. 1993:209-17.

Tahara E, Semba S, Tahara H. Molecular biological observations in gastric cancer. InSeminars in oncology 1996 Jun 1 (Vol. 23, No. 3, pp. 307-315).

Tahara E, Yasui W, Yokozaki H. Abnormal growth factor networks in neoplasia. Cell Proliferation and cancer. Oxford: Oxford University Press. 1996.

Tahara E, editor. Molecular pathology of gastroenterological cancer: application to clinical practice. Springer Science & Business Media; 2013 Jun 29.

Tahara E, Yasui W, Yokozaki H, Shimamoto F. Molecular diagnosis of gastrointestinal cancers: the application to clinical practice. International Journal of Clinical Oncology. 1996 Aug;1:63-8.

Yasui W, Yokozaki H, Tahara E. Molecular diagnosis of gastrointestinal cancer. Molecular Pathology of Gastroenterological Cancer: Application to Clinical Practice. 1997:187-207.

Sahnane N, Magnoli F, Bernasconi B, Tibiletti MG, Romualdi C, Pedroni M, Ponz de Leon M, Magnani G, Reggiani-Bonetti L, Bertario L, Signoroni S. Aberrant DNA methylation profiles of inherited and sporadic colorectal cancer. Clinical epigenetics. 2015 Dec;7:1-2.

Fearon ER. Molecular genetics of colorectal cancer. Annual Review of Pathology: Mechanisms of Disease. 2011 Feb 28;6:479-507.

Grady WM, Markowitz SD. Genetic and epigenetic alterations in colon cancer. Annual review of genomics and human genetics. 2002 Sep;3(1):101-28.

Thakur C, Qiu Y, Fu Y, Bi Z, Zhang W, Ji H, Chen F. Epigenetics and environment in breast cancer: New paradigms for anti-cancer therapies. Frontiers in Oncology. 2022 Sep 15;12:971288.

Locke WJ, Guanzon D, Ma C, Liew YJ, Duesing KR, Fung KY, Ross JP. DNA methylation cancer biomarkers: translation to the clinic. Frontiers in genetics. 2019 Nov 14;10:1150.

Johansson A, Palli D, Masala G, Grioni S, Agnoli C, Tumino R, Giurdanella MC, Fasanelli F, Sacerdote C, Panico S, Mattiello A. Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk. Clinical epigenetics. 2019 Dec;11(1):1-2.

Yegnasubramanian S, Kowalski J, Gonzalgo ML, Zahurak M, Piantadosi S, Walsh PC, Bova GS, De Marzo AM, Isaacs WB, Nelson WG. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer research. 2004 Mar 15;64(6):1975-86.

Yagi M, Kabata M, Ukai T, Ohta S, Tanaka A, Shimada Y, Sugimoto M, Araki K, Okita K, Woltjen K, Hochedlinger K. De novo DNA methylation at imprinted loci during reprogramming into naive and primed pluripotency. Stem Cell Reports. 2019 May 14;12(5):1113-28.

Sun Y, Liu Y, Ma X, Hu H. The influence of cell cycle regulation on chemotherapy. International journal of molecular sciences. 2021 Jun 28;22(13):6923.

Wachsman JT. DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1997 Apr 14;375(1):1-8.

Abbastabar M, Kheyrollah M, Azizian K, Bagherlou N, Tehrani SS, Maniati M, Karimian A. Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein. DNA repair. 2018 Sep 1;69:63-72.

Paige AJ. Redefining tumour suppressor genes: exceptions to the two-hit hypothesis. Cellular and Molecular Life Sciences CMLS. 2003 Oct;60:2147-63.

Hutt JA, Vuillemenot BR, Barr EB, Grimes MJ, Hahn FF, Hobbs CH, March TH, Gigliotti AP, Seilkop SK, Finch GL, Mauderly JL. Life-span inhalation exposure to mainstream cigarette smoke induces lung cancer in B6C3F1 mice through genetic and epigenetic pathways. Carcinogenesis. 2005 Nov 1;26(11):1999-2009.

Belinsky SA. Silencing of genes by promoter hypermethylation: key event in rodent and human lung cancer. Carcinogenesis. 2005 Sep 1;26(9):1481-7.

Zochbauer-Muller S, Fong KM, Maitra A, Lam S, Geradts J, Ashfaq R, Virmani AK, Milchgrub S, Gazdar AF, Minna JD. 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer research. 2001 May 1;61(9):3581-5.

Zöchbauer-Müller S, Fong KM, Virmani AK, Geradts J, Gazdar AF, Minna JD. Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer research. 2001 Jan 1;61(1):249-55.

Lissa D, Ishigame T, Noro R, Tucker MJ, Bliskovsky V, Shema S, Beck JA, Bowman ED, Harris CC, Robles AI. HOXA9 methylation and blood vessel invasion in FFPE tissues for prognostic stratification of stage I lung adenocarcinoma patients. Lung Cancer. 2018 Aug 1;122:151-9.

Boivin AJ, Momparler LF, Hurtubise A, Momparler RL. Antineoplastic action of 5-aza-2′-deoxycytidine and phenylbutyrate on human lung carcinoma cells. Anti-Cancer Drugs. 2002 Sep 1;13(8):869-74.

Bowman RV, Yang IA, Semmler AB, Fong KM. Epigenetics of lung cancer. Respirology. 2006 Jul;11(4):355-65.



How to Cite

Kumar Mahapatra, D. A. P., V. S. Mule, D. A. Naveen, and D. S. Ghosh. “Epigenetics in Cancer Therapy: Oncology-Epigenetics Cancer”. International Journal of Trends in OncoScience, vol. 2, no. 2, Apr. 2024, pp. 32-40, doi:10.22376/ijtos.2024.2.2.32-40.



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