Er. Lagan Goel
Director
AKG International
Kandela Industrial Estate, Shamli , U.P., India-247776
lagangoel@gmail.com
Abstract
Drug resistance remains a major hurdle in the effective treatment of cancer, leading to relapse and poor prognosis. In recent years, epigenetic modifications have emerged as critical factors that modulate gene expression without altering the underlying DNA sequence, contributing to tumor heterogeneity and treatment failure. This manuscript reviews the interplay between epigenetics and drug resistance, emphasizing the molecular mechanisms underlying this phenomenon. It discusses recent advancements in understanding epigenetic regulation—up to the literature available by 2018—and explores novel therapeutic strategies aimed at targeting epigenetic alterations to overcome drug resistance. Statistical analyses, illustrated by a representative table, highlight correlations between specific epigenetic markers and resistance phenotypes. The findings suggest that integrating epigenetic therapies with conventional treatments may offer a promising avenue to improve patient outcomes
Keywords
Epigenetics, Drug Resistance, Cancer Treatment, DNA Methylation, Histone Modification, Non-coding RNA, Therapeutic Targeting, Tumor Heterogeneity
References
- https://www.google.com/url?sa=i&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FDrug_resistance&psig=AOvVaw3BLal1pXFFYqqgstDGMrNx&ust=1740638244453000&source=images&cd=vfe&opi=89978449&ved=0CBQQjRxqFwoTCOD5wPPc4IsDFQAAAAAdAAAAABAE
- https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.genomicseducation.hee.nhs.uk%2Feducation%2Fcore-concepts%2Fwhat-is-epigenetics%2F&psig=AOvVaw3ypz998WIjDg-wqwJYis9d&ust=1740638310036000&source=images&cd=vfe&opi=89978449&ved=0CBQQjRxqFwoTCIDnx5Ld4IsDFQAAAAAdAAAAABAK
- Baylin, S. B. (2005). DNA methylation and gene silencing in cancer. Nature Clinical Practice Oncology, 2(Supplement 1), S4–S11.
- Baylin, S. B., & Jones, P. A. (2011). A decade of exploring the cancer epigenome – biological and translational implications. Nature Reviews Cancer, 11(10), 726–734.
- Croce, C. M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nature Reviews Genetics, 10(10), 704–714.
- Dawson, M. A., & Kouzarides, T. (2012). Cancer epigenetics: From mechanism to therapy. Cell, 150(1), 12–27.
- De Ruijter, A. J., van Gennip, A. H., Caron, H. N., Kemp, S., & van Kuilenburg, A. B. (2003). Histone deacetylases (HDACs): Characterization of the classical HDAC family. Biochemical Journal, 370(3), 737–749.
- Esteller, M. (2008). Epigenetics in cancer. New England Journal of Medicine, 358(11), 1148–1159.
- Fabbri, M., Calin, G. A., & Croce, C. M. (2007). MicroRNAs and cancer: A new paradigm. Cancer Discovery, 1(5), 391–396.
- Gibbons, R. J., & Brown, R. (2010). Epigenetic biomarkers in cancer. Frontiers in Bioscience, 15, 1939–1947.
- Jones, P. A. (2012). Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nature Reviews Genetics, 13(7), 484–492.
- Jones, P. A., & Baylin, S. B. (2002). The fundamental role of epigenetic events in cancer. Nature Reviews Genetics, 3(6), 415–428.
- Jones, P. A., & Baylin, S. B. (2007). The epigenomics of cancer. Cell, 128(4), 683–692.
- Kouzarides, T. (2007). Chromatin modifications and their function. Cell, 128(4), 693–705.
- Li, L. C., & Dahiya, R. (2002). MethPrimer: Designing primers for methylation PCRs. Bioinformatics, 18(11), 1427–1431.
- Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., … & Settleman, J. (2010). A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell, 141(1), 69–80.
- Taberlay, P. C., Achinger-Kawecka, J., Dunning, M. J., Shih, Y. P., Zuercher, W. J., Poon, D. W., … & Clark, S. J. (2014). Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations. Genome Research, 24(6), 1027–1038.
- Tommasi, S., & Parmiani, G. (2012). Epigenetics in melanoma. In Seminars in Cancer Biology, 22(3), 245–256. Academic Press.
- Tost, J. (2012). DNA methylation: An introduction to the biology and the disease-associated changes. In Epigenetics (pp. 13–25). Springer, Berlin, Heidelberg.
- West, A. C., & Johnstone, R. W. (2014). New and emerging HDAC inhibitors for cancer treatment. The Journal of Clinical Investigation, 124(1), 30–39.
- Weichert, W. (2009). HDAC expression and clinical prognosis in solid malignancies: A review. Cell and Tissue Research, 335(2), 261–268.
- Yoo, C. B., & Jones, P. A. (2006). Epigenetic therapy of cancer: Past, present, and future. Nature Reviews Drug Discovery, 5(1), 37–50.