The role of DNA methylation and histone modifications in the pathogenesis of hematological malignancies and solid cancers: mechanisms, clinical implications, and therapeutic potential

Authors

DOI:

https://doi.org/10.3329/ajmbr.v11i2.79668

Keywords:

epigenetics, gene silencing, therapeutic biomarkers, cancer stem cells, cancer therapy

Abstract

Epigenetic changes are increasingly acknowledged as crucial factors in the beginning of both blood cancers and solid tumors. These amendments, such as DNA methylation and histone changes, influence gene expression and cellular activities without altering the fundamental DNA sequence. This review aims to provide a comprehensive analysis of the role of DNA methylation and histone modifications in cancer pathogenesis, with a focus on their potential applications as diagnostic, prognostic, and therapeutic biomarkers. The review synthesizes findings from recent studies on epigenetic alterations in cancer, emphasizing their mechanistic roles in tumorigenesis, therapeutic resistance, and tumor heterogeneity. Relevant studies were chosen for their focus on DNA methylation, histone modifications, and their clinical significance. This review highlights the frequent occurrence of tumor suppressor gene hypermethylation and oncogene hypomethylation across various cancers. Additionally, changes in histone modifications, such as acetylation, methylation, and phosphorylation, can alter chromatin configuration and play a significant role in the emergence of oncogenic characteristics. The crosstalk between these epigenetic mechanisms contributes to the reprogramming of the cancer epigenome, driving tumor heterogeneity and resistance to therapy. Understanding the mechanisms of epigenetic alterations in cancer provides new opportunities for developing targeted therapies and improving patient outcomes. Epigenetic biomarkers hold promise for early diagnosis, prognosis, and personalized treatment strategies.  This review underscores the importance of epigenetic research in oncology, offering insights into novel therapeutic targets and strategies. It also highlights the need for further studies to translate these findings into clinical applications, ultimately reshaping cancer treatment paradigms.

Asian J. Med. Biol. Res. 2025, 11(2), 23-36

Downloads

Abstract
109
PDF
190

References

Azaïs H, S Garinet, L Benoit, J de Jesus, M Zizi, S Landman, AS Bats, V Taly, P Laurent-Puig and H Blons, 2024. Prognostic value of BRCA1 promoter methylation for patients with epithelial ovarian cancer. J. Gynecol. Obstet. Hum. Reprod., 53: 102796.

Bestor TH, 1992. Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. EMBO J., 11: 2611-2617.

Bhartiya D, S Raouf, K Pansare, A Tripathi and A Tripathi, 2024. Initiation of cancer: the journey from mutations in somatic cells to epigenetic changes in tissue-resident VSELs. Stem Cell Rev. Rep., 20: 857-880.

Bruno PS, A Arshad, MR Gogu, N Waterman, R Flack, K Dunn, CC Darie and AN Neagu, 2025. Post-translational modifications of proteins orchestrate all hallmarks of cancer. Life, 15: 126.

Chen F, X He, W Xu, L Zhou, Q Liu, W Chen, WG Zhu and J Zhang, 2024a. Chromatin lysine acylation: on the path to chromatin homeostasis and genome integrity. Cancer Sci., 115: 3506-3519.

Chen X, AS Agustinus, J Li, M DiBona and SF Bakhoum, 2024b. Chromosomal instability as a driver of cancer progression. Nat. Rev. Genet., 26: 31-46.

Chen Y, R Liang, Y Li, L Jiang, D Ma, Q Luo and G Song, 2024c. Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application. Signal Transduct. Target Ther., 9: 340.

Chen Z, C Li, Y Zhou, P Li, G Cao, Y Qiao, Y Yao and J Su, 2024d. Histone 3 lysine 9 acetylation-specific reprogramming regulates esophageal squamous cell carcinoma progression and metastasis. Cancer Gene Ther., 31: 612-626.

Dakal TC, B Dhabhai, A Pant, K Moar, K Chaudhary, V Yadav, V Ranga, NK Sharma, A Kumar, PK Maurya and J Maciaczyk, 2024. Oncogenes and tumor suppressor genes: functions and roles in cancers. MedComm, 5: e582.

Das A, AK Giri and P Bhattacharjee, 2024. Targeting ‘histone mark’: advanced approaches in epigenetic regulation of telomere dynamics in cancer. Biochim. Biophys. Acta. Gene Regul. Mech., 1867: 195007.

De Plano LM, A Saitta, S Oddo and A Caccamo, 2024. Epigenetic changes in Alzheimer’s disease: DNA methylation and histone modification. Cells, 13: 719.

De Riso G, V Naef, D Damiani, S Doccini, FM Santorelli and D Galatolo, 2025. Whole blood DNA methylation analysis reveals epigenetic changes associated with ARSACS. Cerebellum, 24: 36.

Delphin N, C Aust, L Griffiths and F Fernandez, 2024. Epigenetic regulation in schizophrenia: focus on methylation and histone modifications in human studies. Genes, 15: 272.

El Omari N, S Bakrim, M Bakha, A Balahbib, A Bouyahya, C Ardianto, LC Ming and HL Ser, 2025. DNA methylation: its role and interaction with epigenetic modifications in cancer. Prog. Micro. Mol. Biol., 8: a0000458.

El-Tanani M, SA Rabbani, SM Satyam, IR Rangraze, AF Wali, Y El-Tanani and AA Aljabali, 2025. Deciphering the role of cancer stem cells: drivers of tumor evolution, therapeutic resistance, and precision medicine strategies. Cancers, 17: 382.

Farshadi F, 2024. Characterization and validation of PITX2 and TGM2 methylation in HPV-related head and neck squamous cell carcinoma. MSc thesis, Department of Medicine, Division of experimental Medicine, McGill University, Montréal, Canada. pp. 1-85.

Fatma H and HR Siddique, 2024. Cancer cell plasticity, stem cell factors, and therapy resistance: how are they linked? Cancer Metastasis Rev., 43: 423-440.

Garg P, J Malhotra, P Kulkarni, D Horne, R Salgia and SS Singhal, 2024. Emerging therapeutic strategies to overcome drug resistance in cancer cells. Cancers, 16: 2478.

Griñán-Ferré C, A Bellver-Sanchis, A Guerrero and M Pallàs, 2024. Advancing personalized medicine in neurodegenerative diseases: the role of epigenetics and pharmacoepigenomics in pharmacotherapy. Pharmacol. Res., 205: 107247.

Grozinger CM and SL Schreiber, 2002. Deacetylase enzymes: biological functions and the use of small-molecule inhibitors. Chem. Biol., 9: 3-16.

Gu M, B Ren, Y Fang, J Ren, X Liu, X Wang, F Zhou, R Xiao, X Luo, L You and Y Zhao, 2024. Epigenetic regulation in cancer. MedComm., 5: e495.

Gu Y, R Yang, Y Zhang, M Guo, K Takehiro, M Zhan, L Yang and H Wang, 2025. Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer. Mol. Biomed., 6: 2.

Gupta I, F Badrzadeh, Y Tsentalovich and DA Gaykalova, 2024. Connecting the dots: investigating the link between environmental, genetic, and epigenetic influences in metabolomic alterations in oral squamous cell carcinoma. J. Exp. Clin. Cancer Res., 43: 239.

Han R, D Zhu, J Sha, B Zhao, P Jin and C Meng, 2024. Decoding the role of DNA methylation in allergic diseases: from pathogenesis to therapy. Cell Biosci., 14: 89.

Hojjatipour T, M Ajeli, A Maali and M Azad, 2024. Epigenetic-modifying agents: the potential game changers in the treatment of hematologic malignancies. Crit. Rev. Oncol. Hematol., 6: 104498.

Huang P, F Wen, Y Li and Q Li, 2024. The tale of SOX2: Focusing on lncRNA regulation in cancer progression and therapy. Life Sci., 344: 122576.

Ji Y, B Li, R Lin, J Yuan, Y Han, Y Du and Y Zhao, 2025. Super-enhancers in tumors: Unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies. J. Transl. Med., 23: 98.

Jones PA and SB Baylin, 2002. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet., 3: 415-428.

Joshi G and A Basu, 2024. Epigenetic control of cell signalling in cancer stem cells. Int. Rev. Cell Mol. Biol., 383: 67-88.

Kawaf RR, WS Ramadan and R El-Awady, 2024. Deciphering the interplay of histone post-translational modifications in cancer: co-targeting histone modulators for precision therapy. Life Sci., 346: 122639.

Khabbazpour M, M Tat, A Karbasi, MA Abyazi, G Khodadoustan, Z Heidary and M Zaki-Dizaji, 2024. Advances in blood DNA methylation-based assay for colorectal cancer early detection: a systematic updated review. Gastroenterol. Hepatol. Bed Bench, 17: 225-240.

Khan AQ, A Hasan, SS Mir, K Rashid, S Uddin and M Stienhoff, 2024. Exploiting transcription factors to target EMT and cancer stem cells for tumor modulation and therapy. Semin. Cancer Biol., 100: 1-16.

Kiri S and T Ryba, 2024. Cancer, metastasis, and the epigenome. Mol. Cancer, 23: 154.

Lee AV, KA Nestler and KB Chiappinelli, 2024. Therapeutic targeting of DNA methylation alterations in cancer. Pharmacol. Ther., 258: 108640.

Lei ZN, QX Teng , J Koya, Y Liu, Z Chen, L Zeng, ZS Chen, S Fang, J Wang, Y Liu and Y Pan, 2024. The correlation between cancer stem cells and epithelial-mesenchymal transition: molecular mechanisms and significance in cancer theragnosis. Front. immunol., 15: 1417201.

Li N, K Song, H Chen and M Dai, 2025. Advance and challenge of DNA methylation as cancer biomarkers for risk stratification, screening and early detection. J. Natl. Cancer Cent., 5: 5.

Li X, C Liu, Z Lei, H Chen and L Wang, 2024. Phase-separated chromatin compartments: orchestrating gene expression through condensation. Cell Insight, 3: 100213.

Liang BB, YH Wang, JJ Huang, S Lin, GC Mao, ZJ Zhou, WJ Yan, CY Shan, HZ Wu, A Etcheverry and YL He, 2024. Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non‐G‐CIMP glioblastomas with unmethylated MGMT promoter: MGMT‐dependent roles of GPR81. CNS Neurosci. Ther., 30: e14465.

López-Hernández L, P Toolan-Kerr, AJ Bannister and G Millán-Zambrano, 2025. Dynamic histone modification patterns coordinating DNA processes. Mol. Cell., 85: 225-237.

Lossi L, C Castagna and A Merighi, 2024. An overview of the epigenetic modifications in the brain under normal and pathological conditions. Int. J. Mol. Sci., 25: 3881.

Ma H, J Qu, Z Pang, J Luo, M Yan, W Xu, H Zhuang, L Liu and Q Qu, 2024. Super-enhancer omics in stem cell. Mol. Cancer., 23: 153.

Marks PA and WS Xu, 2009. Histone deacetylase inhibitors: potential in cancer therapy. J. Cell Biochem., 107: 600-608.

Marques D, N Vaziri, SC Greenway and C Bousman, 2024. DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review. Mol. Psychiatry, 30: 296-309.

Merz AMA, M Sébert, J Sonntag, AS Kubasch, U Platzbecker and L Adès, 2024. Phase to phase: Navigating drug combinations with hypomethylating agents in higher-risk MDS trials for optimal outcomes. Cancer Treat. Rev., 123: 102673.

Miziak P, M Baran, L Borkiewicz, T Trombik and A Stepulak, 2024. Acetylation of histone H3 in cancer progression and prognosis. Int. J. Mol. Sci., 25: 10982.

Molefi T, L Mabonga, R Hull, M Sebitloane and Z Dlamini, 2025. From genes to clinical practice: exploring the genomic underpinnings of endometrial cancer. Cancers, 17: 320.

Muletier R, C Bourgne, L Guy and A Dougé, 2025. DNA methylation in prostate cancer: clinical implications and potential applications. Cancer Med., 14: e70528.

Mungly SB, EP Peter, LW Hii, CW Mai and FF Chung, 2024. Epigenetic drug interventions in breast cancer: a narrative review of current research and future directions. Prog. Micro. Mol. Biol., 7: a0000448.

Muthukumar S, CT Li, RJ Liu and C Bellodi, 2024. Roles and regulation of tRNA-derived small RNAs in animals. Nat. Rev. Mol. Cell Biol., 25: 359-378.

Nagasaka K, 2024. Clonal evolution and molecular mechanisms of ovarian cancer: a comprehensive review. Acad. Oncol., 1: 1-18.

Okano M, DW Bell, DA Haber and E Li, 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99: 247-257.

Pan J, S Chen, X Chen, Y Song and H Cheng, 2025. Histone modifications and DNA methylation in psoriasis: a cellular perspective. Clin. Rev. Allergy Immunol., 68: 6.

Pan S, T Yuan, Y Xia, W Yu, X Zhou and F Cheng, 2024. Role of histone modifications in kidney fibrosis. Medicina, 60: 888.

Pandey P, F Khan, M Singh, A Verma, H Kumar, A Mazumder and G Rakhra, 2024. Study deciphering the crucial involvement of Notch signaling pathway in human cancers. Endocr. Metab. Immune. Disord. Drug Targets, 24: 1241-1253.

Pappalardo XG and V Barra, 2021. Losing DNA methylation at repetitive elements and breaking bad. Epigenetics Chromatin, 14: 25.

Parikh D and M Shah, 2024. A comprehensive study on epigenetic biomarkers in early detection and prognosis of Alzheimer's disease. Biomedical Analysis, 1: 138-153.

Prabhu KS, HQ Sadida, S Kuttikrishnan, K Junejo, AA Bhat and S Uddin, 2024. Beyond genetics: exploring the role of epigenetic alterations in breast cancer. Pathol. Res. Pract., 254: 155174.

Qian Z, Y Jiang, Y Wang, Y Li, L Zhang, X Xu and D Chen, 2025. DNA methylation of ACADS promotes immunogenic cell death in hepatocellular carcinoma. Cell Biosci., 15: 3.

Rahimi-Farsi N, F Bostanian, T Shahbazi, FS Shamsinejad, M Bolideei, P Mohseni, A Zangooie, F Boustani and H Shoorei, 2025. Novel oncogenes and tumor suppressor genes in hepatocellular carcinoma: carcinogenesis, progression, and therapeutic targets. Gene, 941: 149229.

Rajendran P, M Prasad, EM, Ali, R Sekar, AM AlZahrani, MI Karobari, MA Genena and BM Abdallah, 2025. Molecular insight into histone methylation as a novel target for oral squamous cell carcinoma: future hope in personalised medicine. J. Cancer, 16: 1575-1590.

Ramazi S, M Dadzadi, Z Sahafnejad and A Allahverdi, 2024. Histone modification and personalized epigenomics in cancer. In: Personalized Epigenetics. Edited by: Trygve T, Academic Press, pp. 429-473.

Roy P, R Kandel, N Sawant and KP Singh, 2024. Estrogen-induced reactive oxygen species, through epigenetic reprogramming, causes increased growth in breast cancer cells. Mol. Cell. Endocrinol., 579: 112092.

Ruszkowska-Ciastek B, K Kwiatkowska, D Marques-da-Silva and R Lagoa, 2024. Cancer stem cells from definition to detection and targeted drugs. Int. J. Mol. Sci., 25: 3903.

Sadida HQ, A Abdulla, S Al Marzooqi, S Hashem, MA Macha, AS Akil and AA Bhat, 2024. Epigenetic modifications: key players in cancer heterogeneity and drug resistance. Transl. Oncol., 39: 101821.

Sadri F, S fatemeh Hosseini, Z Rezaei and M Fereidouni, 2024. Hippo-YAP/TAZ signaling in breast cancer: reciprocal regulation of microRNAs and implications in precision medicine. Genes Dis., 11: 760-71.

Shaalan F, N Ballout and WT Chamoun, 2025. Insights into the role of Bmi-1 deregulation in promoting stemness and therapy resistance in glioblastoma: a narrative review. Cancer Med., 14: e70566.

Shaik R, MS Malik, S Basavaraju, J Qurban, FM Al-Subhi, S Badampudi, J Peddapaka, A Shaik, A Abd-El-Aziz, Z Moussa and SA Ahmed, 2025. Cellular and molecular aspects of drug resistance in cancers. DARU J. Pharm. Sci., 33: 4.

Sinha J, JF Nickels, AR Thurm, CH Ludwig, BN Archibald, MM Hinks, J Wan, D Fang and L Bintu, 2024. The H3.3K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation. Mol. Cell, 84: 3899-3915.

Sriwastava AK, 2025. Role of epigenetics in breast cancer: current status and future perspectives. In: Advances in Cancer Biomarkers Research. Edited by: Singh AN, R Rana and S Nayak, Elsevier, pp. 191-204.

Su B, S Li, S Geng, D Brambilla, R Sun, T Sun and C Jiang, 2024. Therapeutic regulation of epigenetics in cancer treatment through drug delivery systems. Nano Today, 56: 102251.

Temitope OT, OT Ifeoluwa, AS Adegbola, AJ Oluwatosin, AA Daniel, NA Joy, OD Ebubechi, ANL Kenneth, AA Augustine, AK Gbenga, AA Rapheal, EM Ibilola and AO Goodluck, 2025. Epigenomic profiling in cancer: techniques and therapeutic implications. Int. J. Adv. Biol. Biome. Res., 13: 90-116.

Tonti E, R Dell’Omo, M Filippelli, L Spadea, C Salati, C Gagliano, M Musa and M Zeppieri, 2024. Exploring epigenetic modifications as potential biomarkers and therapeutic targets in glaucoma. Int. J. Mol. Sci., 25: 2822.

Wang D, Y Zhang, Q Li, Y Li, W Li, A Zhang, J Xu, J Meng, L Tang and S Lyu, 2024a. Epigenetics: mechanisms, potential roles, and therapeutic strategies in cancer progression. Genes Dis., 11: 101020.

Wang H, B Liu, H Chen, P Xu, H Xue and J Yuan, 2023. Dynamic changes of DNA methylation induced by benzo (a) pyrene in cancer. Genes Environ., 45: 21.

Wang X, X Teng, C Luo and L Kong, 2024b. Mechanisms and advances of epigenetic regulation in cardiovascular disease. Front. Biosci., 29: 205.

Wong LH and DJ Tremethick, 2024. Multifunctional histone variants in genome function. Nat. Rev. Genet., 26: 82-104.

Xie H, W Yin, Y Zheng, Y Zhang, H Qin, Z Huang, M Zhao and J Li, 2024. Increased DNA methylation of the splicing regulator SR45 suppresses seed abortion in litchi. J. Exp. Bot., 75: 868-882.

Xu Z, J Shi, Q Chen, S Yang, Z Wang, B Xiao, Z Lai, Y Jing, Y Li and X Li, 2025. Regulation of de novo and maintenance DNA methylation by DNA methyltransferases in postimplantation embryos. J. Biol. Chem., 301: 107990.

Yang F, Y Yang, Y Qiu, L Tang, L Xie and X Guan, 2024. Long non-coding RNAs as regulators for targeting breast cancer stem cells and tumor immune microenvironment: biological properties and therapeutic potential. Cancers, 16: 290.

Yao W, X Hu and X Wang, 2024. Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases. Sig. Transduct. Target Ther., 9: 232.

Yu H and BJ Lesch, 2024a. Functional roles of H3K4 methylation in transcriptional regulation. Mol. Cell Biol., 44: 505-515.

Yu X, J Yang, J Xu, H Pan, W Wang, X Yu and S Shi, 2024b. Histone lactylation: from tumor lactate metabolism to epigenetic regulation. Int. J. Biol. Sci., 20: 1833–1854.

Zakari S, NK Niels, GV Olagunju, PC Nnaji, O Ogunniyi, M Tebamifor, EN Israel, SE Atawodi and OO Ogunlana, 2024. Emerging biomarkers for non-invasive diagnosis and treatment of cancer: a systematic review. Front. Oncol., 14: 1405267.

Zhang J, Z Tian, C Qin and MR Momeni, 2024. The effects of exercise on epigenetic modifications: focus on DNA methylation, histone modifications and non-coding RNAs. Hum. Cell, 37: 887-903.

Zhao N, C Lai, Y Wang, S Dai and H Gu, 2024. Understanding the role of DNA methylation in colorectal cancer: mechanisms, detection, and clinical significance. Biochim. Biophys. Acta Rev. Cancer, 1879: 189096.

Zhu Q, J Xie, W Mei and C Zeng, 2024. Methylated circulating tumor DNA in hepatocellular carcinoma: a comprehensive analysis of biomarker potential and clinical implications. Cancer Treat. Rev., 128: 102763.

Downloads

Published

2025-04-14

How to Cite

Ur Rehman, S., Abdullah, M., Khan, Z. K., & Shurovi, M. (2025). The role of DNA methylation and histone modifications in the pathogenesis of hematological malignancies and solid cancers: mechanisms, clinical implications, and therapeutic potential. Asian Journal of Medical and Biological Research, 11(2), 23–36. https://doi.org/10.3329/ajmbr.v11i2.79668

Issue

Section

Review Articles