The Role of Epigenetic Modifications in Cancer Development and Progression: Potential Therapeutic Approaches
DOI:
https://doi.org/10.70749/ijbr.v3i1.635Keywords:
Epigenetic Modifications, Cancer Progression, DNMT Inhibitors, HDAC Inhibitors, miRNAs, CRISPR, Gene Editing, Therapeutic EfficacyAbstract
This research sought to explore the role of epigenetic changes in cancer initiation and progression, the therapeutic potential of epigenetic modulators, i.e., DNMT inhibitors and HDAC inhibitors, and the expression levels of non-coding RNAs, i.e., miRNAs, in controlling epigenetic changes in cancer cells. The research used a quantitative method, i.e., structured questionnaires and regression analysis to determine the role of epigenetic changes in cancer biology. The research validated that 65% of the respondents were familiar with DNA methylation, 60% with histone modification, and 55% with gene-editing technologies like CRISPR. The Chi-Square analysis validated the presence of significant disparity in awareness among demographic groups, with p-values of 0.02 and 0.05 for awareness of DNA methylation by age and awareness of histone modification by medical specialty, respectively. Regression analysis validated that DNMT inhibitors significantly caused cancer cell apoptosis (β = 0.55, p = 0.0002) and suppressed cancer cell migration (β = -0.30, p = 0.02), while HDAC inhibitors also caused apoptosis (β = 0.47, p = 0.005) and promoted migration inhibition (β = -0.25, p = 0.03). The Chi-Square test of expression of miRNAs further validated significant correlations between miR-21 expression and cancer type (χ² = 10.4, p = 0.02) and between miR-34a expression and DNA methylation (χ² = 12.1, p = 0.01). These results suggest the potential of epigenetic therapies and miRNA-based therapies in controlling cancer cell behavior and enhancing therapeutic efficacy. This study highlights epigenetic modifications in cancer, the potential of DNMT and HDAC inhibitors, and miRNAs, urging further research on optimization.
Downloads
References
Fardi, M., Solali, S., & Farshdousti Hagh, M. (2018). Epigenetic mechanisms as a new approach in cancer treatment: An updated review. Genes & Diseases, 5(4), 304-311. https://doi.org/10.1016/j.gendis.2018.06.003
Mohammad, H. P., Barbash, O., & Creasy, C. L. (2019). Targeting epigenetic modifications in cancer therapy: Erasing the roadmap to cancer. Nature Medicine, 25(3), 403-418. https://doi.org/10.1038/s41591-019-0376-8
Rius, M., & Lyko, F. (2011). Epigenetic cancer therapy: Rationales, targets and drugs. Oncogene, 31(39), 4257-4265. https://doi.org/10.1038/onc.2011.601
Kanwal, R., & Gupta, S. (2011). Epigenetic modifications in cancer. Clinical Genetics, 81(4), 303-311. https://doi.org/10.1111/j.1399-0004.2011.01809.x
Kelly, T. K., De Carvalho, D. D., & Jones, P. A. (2010). Epigenetic modifications as therapeutic targets. Nature Biotechnology, 28(10), 1069-1078. https://doi.org/10.1038/nbt.1678
Thomas, M., & Marcato, P. (2018). Epigenetic modifications as biomarkers of tumor development, therapy response, and recurrence across the cancer care continuum. Cancers, 10(4), 101. https://doi.org/10.3390/cancers10040101
Neganova, M. E., Klochkov, S. G., Aleksandrova, Y. R., & Aliev, G. (2022). Histone modifications in epigenetic regulation of cancer: Perspectives and achieved progress. Seminars in Cancer Biology, 83, 452-471. https://doi.org/10.1016/j.semcancer.2020.07.015
Pruitt, K. (2016). Molecular and cellular changes during cancer progression resulting from genetic and epigenetic alterations. Progress in Molecular Biology and Translational Science, 3-47. https://doi.org/10.1016/bs.pmbts.2016.09.001
Gracia-Hernandez, M., Munoz, Z., & Villagra, A. (2021). Enhancing therapeutic approaches for melanoma patients targeting epigenetic modifiers. Cancers, 13(24), 6180. https://doi.org/10.3390/cancers13246180
Vaiopoulos, A. G., Athanasoula, K. C., & Papavassiliou, A. G. (2014). Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1842(7), 971-980. https://doi.org/10.1016/j.bbadis.2014.02.006
Tan, T., Shi, P., Abbas, M., Wang, Y., Xu, J., Chen, Y., & Cui, H. (2022). Epigenetic modification regulates tumor progression and metastasis through EMT (Review). International Journal of Oncology, 60(6). https://doi.org/10.3892/ijo.2022.5360
Saleh, R., Toor, S. M., Sasidharan Nair, V., & Elkord, E. (2020). Role of epigenetic modifications in inhibitory immune checkpoints in cancer development and progression. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.01469
Nirmaladevi, R. (2020). Epigenetic alterations in cancer. Frontiers in Bioscience, 25(6), 1058-1109. https://doi.org/10.2741/4847
Patnaik, S., & Anupriya. (2019). Drugs targeting epigenetic modifications and plausible therapeutic strategies against colorectal cancer. Frontiers in Pharmacology, 10. https://doi.org/10.3389/fphar.2019.00588
Bhol, C. S., Panigrahi, D. P., Praharaj, P. P., Mahapatra, K. K., Patra, S., Mishra, S. R., Behera, B. P., & Bhutia, S. K. (2020). Epigenetic modifications of autophagy in cancer and cancer therapeutics. Seminars in Cancer Biology, 66, 22-33. https://doi.org/10.1016/j.semcancer.2019.05.020
Castro Muñoz, L., Ulloa, E., Sahlgren, C., Lizano, M., De La Cruz-Hernández, E., & Contreras Paredes, A. (2023). Modulating epigenetic modifications for cancer therapy (Review). Oncology Reports, 49(3). https://doi.org/10.3892/or.2023.8496
Sadida, H. Q., Abdulla, A., Marzooqi, S. A., Hashem, S., Macha, M. A., Akil, A. S., & Bhat, A. A. (2024). Epigenetic modifications: Key players in cancer heterogeneity and drug resistance. Translational Oncology, 39, 101821. https://doi.org/10.1016/j.tranon.2023.101821
Perri, F., Longo, F., Giuliano, M., Sabbatino, F., Favia, G., Ionna, F., Addeo, R., Della Vittoria Scarpati, G., Di Lorenzo, G., & Pisconti, S. (2017). Epigenetic control of gene expression: Potential implications for cancer treatment. Critical Reviews in Oncology/Hematology, 111, 166-172. https://doi.org/10.1016/j.critrevonc.2017.01.020
Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016). Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nature Reviews Genetics, 17(5), 284-299. https://doi.org/10.1038/nrg.2016.13
Coyle, K. M., Boudreau, J. E., & Marcato, P. (2017). Genetic mutations and epigenetic modifications: Driving cancer and informing precision medicine. BioMed Research International, 2017, 1-18. https://doi.org/10.1155/2017/9620870
Karami Fath, M., Azargoonjahromi, A., Kiani, A., Jalalifar, F., Osati, P., Akbari Oryani, M., Shakeri, F., Nasirzadeh, F., Khalesi, B., Nabi-Afjadi, M., Zalpoor, H., Mard-Soltani, M., & Payandeh, Z. (2022). The role of epigenetic modifications in drug resistance and treatment of breast cancer. Cellular & Molecular Biology Letters, 27(1). https://doi.org/10.1186/s11658-022-00344-6
Rezapour, S., Hosseinzadeh, E., Marofi, F., & Hassanzadeh, A. (2019). Epigenetic‐based therapy for colorectal cancer: Prospect and involved mechanisms. Journal of Cellular Physiology, 234(11), 19366-19383. https://doi.org/10.1002/jcp.28658
Chakravarthi, B. V., Nepal, S., & Varambally, S. (2016). Genomic and Epigenomic alterations in cancer. The American Journal of Pathology, 186(7), 1724-1735. https://doi.org/10.1016/j.ajpath.2016.02.023
Ellis, L., Atadja, P. W., & Johnstone, R. W. (2009). Epigenetics in cancer: Targeting chromatin modifications. Molecular Cancer Therapeutics, 8(6), 1409-1420. https://doi.org/10.1158/1535-7163.mct-08-0860
Mondal, P., Natesh, J., Penta, D., & Meeran, S. M. (2022). Progress and promises of epigenetic drugs and epigenetic diets in cancer prevention and therapy: A clinical update. Seminars in Cancer Biology, 83, 503-522. https://doi.org/10.1016/j.semcancer.2020.12.006
Zaib, S., Rana, N., & Khan, I. (2022). Histone modifications and their role in epigenetics of cancer. Current Medicinal Chemistry, 29(14), 2399-2411. https://doi.org/10.2174/0929867328666211108105214
Song, S., Han, S., & Bang, Y. (2011). Epigenetic-based therapies in cancer. Drugs, 71(18), 2391-2403. https://doi.org/10.2165/11596690-000000000-00000
Herranz, M., & Esteller, M. (n.d.). DNA methylation and histone modifications in patients with cancer: Potential prognostic and therapeutic targets. Target Discovery and Validation Reviews and Protocols, 25-62. https://doi.org/10.1385/1-59745-208-4:25
Nebbioso, A., Tambaro, F. P., Dell’Aversana, C., & Altucci, L. (2018). Cancer epigenetics: Moving forward. PLOS Genetics, 14(6), e1007362. https://doi.org/10.1371/journal.pgen.1007362
Angulo, J. C., Manini, C., López, J. I., Pueyo, A., Colás, B., & Ropero, S. (2021). The role of epigenetics in the progression of clear cell renal cell carcinoma and the basis for future epigenetic treatments. Cancers, 13(9), 2071. https://doi.org/10.3390/cancers13092071
Vecchio, L., Seke Etet, P. F., Kipanyula, M. J., Krampera, M., & Nwabo Kamdje, A. H. (2013). Importance of epigenetic changes in cancer etiology, pathogenesis, clinical profiling, and treatment: What can be learned from hematologic malignancies? Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1836(1), 90-104. https://doi.org/10.1016/j.bbcan.2013.04.001
Herceg, Z., & Hainaut, P. (2007). Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Molecular Oncology, 1(1), 26-41. https://doi.org/10.1016/j.molonc.2007.01.004
Prabhu, K. S., Sadida, H. Q., Kuttikrishnan, S., Junejo, K., Bhat, A. A., & Uddin, S. (2024). Beyond genetics: Exploring the role of epigenetic alterations in breast cancer. Pathology - Research and Practice, 254, 155174. https://doi.org/10.1016/j.prp.2024.155174
Hessmann, E., Johnsen, S. A., Siveke, J. T., & Ellenrieder, V. (2016). Epigenetic treatment of pancreatic cancer: Is there a therapeutic perspective on the horizon? Gut, 66(1), 168-179. https://doi.org/10.1136/gutjnl-2016-312539
Verma, M., & Srivastava, S. (2002). Epigenetics in cancer: Implications for early detection and prevention. The Lancet Oncology, 3(12), 755-763. https://doi.org/10.1016/s1470-2045(02)00932-4
Davalos, V., & Esteller, M. (2022). Cancer epigenetics in clinical practice. CA: A Cancer Journal for Clinicians, 73(4), 376-424. https://doi.org/10.3322/caac.21765
Bouyahya, A., Mechchate, H., Oumeslakht, L., Zeouk, I., Aboulaghras, S., Balahbib, A., Zengin, G., Kamal, M. A., Gallo, M., Montesano, D., & El Omari, N. (2022). The role of epigenetic modifications in human cancers and the use of natural compounds as Epidrugs: Mechanistic pathways and Pharmacodynamic actions. Biomolecules, 12(3), 367. https://doi.org/10.3390/biom12030367
Hillyar, C., Rallis, K. S., & Varghese, J. (2020). Advances in epigenetic cancer therapeutics. Cureus. https://doi.org/10.7759/cureus.11725
Dhanak, D., & Jackson, P. (2014). Development and classes of epigenetic drugs for cancer. Biochemical and Biophysical Research Communications, 455(1-2), 58-69. https://doi.org/10.1016/j.bbrc.2014.07.006
Amodio, N., D’Aquila, P., Passarino, G., Tassone, P., & Bellizzi, D. (2016). Epigenetic modifications in multiple myeloma: Recent advances on the role of DNA and histone methylation. Expert Opinion on Therapeutic Targets, 21(1), 91-101. https://doi.org/10.1080/14728222.2016.1266339
Falahi, F., Van Kruchten, M., Martinet, N., Hospers, G., & Rots, M. G. (2014). Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer. Breast Cancer Research, 16(4). https://doi.org/10.1186/s13058-014-0412-z
Ponnusamy, L., Mahalingaiah, P. K., & Singh, K. P. (2020). Epigenetic reprogramming and potential application of epigenetic-modifying drugs in acquired chemotherapeutic resistance. Advances in Clinical Chemistry, 219-259. https://doi.org/10.1016/bs.acc.2019.07.011
Lyko, F., & Brown, R. (2005). DNA Methyltransferase inhibitors and the development of epigenetic cancer therapies. JNCI: Journal of the National Cancer Institute, 97(20), 1498-1506. https://doi.org/10.1093/jnci/dji311
Burkitt, K., & Saloura, V. (2021). Epigenetic modifiers as novel therapeutic targets and a systematic review of clinical studies investigating epigenetic inhibitors in head and neck cancer. Cancers, 13(20), 5241. https://doi.org/10.3390/cancers13205241
Pfister, S. X., & Ashworth, A. (2017). Marked for death: Targeting epigenetic changes in cancer. Nature Reviews Drug Discovery, 16(4), 241-263. https://doi.org/10.1038/nrd.2016.256
Sharma, S., Kelly, T. K., & Jones, P. A. (2009). Epigenetics in cancer. Carcinogenesis, 31(1), 27-36. https://doi.org/10.1093/carcin/bgp220
Munteanu, R., Tomuleasa, C., Iuga, C., Gulei, D., & Ciuleanu, T. E. (2023). Exploring therapeutic avenues in lung cancer: The epigenetic perspective. Cancers, 15(22), 5394. https://doi.org/10.3390/cancers15225394
Valdespino-Gomez, V. M., & Valdespino, P. M. (2015). Potential of epigenetic therapies in the management of solid tumors. Cancer Management and Research, 241. https://doi.org/10.2147/cmar.s70358
Einav Nili, G., Saito, Y., Egger, G., & Jones, P. A. (2008). Cancer epigenetics: Modifications, screening, and therapy. Annual Review of Medicine, 59(1), 267-280. https://doi.org/10.1146/annurev.med.59.061606.095816
Teh, B. T., & Fearon, E. R. (2020). Genetic and epigenetic alterations in cancer. Abeloff's Clinical Oncology, 209-224.e2. https://doi.org/10.1016/b978-0-323-47674-4.00014-1
Adwan, L., & Zawia, N. H. (2013). Epigenetics: A novel therapeutic approach for the treatment of Alzheimer's disease. Pharmacology & Therapeutics, 139(1), 41-50. https://doi.org/10.1016/j.pharmthera.2013.03.010
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Indus Journal of Bioscience Research

This work is licensed under a Creative Commons Attribution 4.0 International License.