Commentary - (2025) Volume 9, Issue 6
Received: 01-Nov-2025, Manuscript No. jgdr-26-179217;
Editor assigned: 03-Nov-2025, Pre QC No. P-179217;
Reviewed: 17-Nov-2025, QC No. Q-179217;
Revised: 24-Nov-2025, Manuscript No. R-179217;
Published:
29-Nov-2025
, DOI: 10.37421/2684-6039.2025.09.297
Citation: Torres-Vega, Miguel. ”Epigenetics: Drivers of Cancer, Therapy and Biomarkers.” J Genet DNA Res 09 (2025):297.
Copyright: © 2025 Torres-Vega M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Epigenomic alterations represent fundamental drivers of cancer development, profoundly influencing gene expression without altering the underlying DNA sequence. These dynamic changes encompass a range of modifications, including DNA methylation, histone modifications, and the involvement of non-coding RNAs, which collectively define the epigenomic landscape. Aberrant patterns within these epigenetic marks have the capacity to silence critical tumor suppressor genes, conversely activate oncogenes, and contribute significantly to genomic instability. Ultimately, these disruptions promote tumor initiation, drive disease progression, and can confer resistance to therapeutic interventions. A thorough understanding of these dynamic epigenetic changes offers highly promising avenues for the identification of novel diagnostic biomarkers and the development of innovative therapeutic strategies that specifically target epigenetic pathways[1].
DNA methylation, recognized as a key epigenetic modification, plays a pivotal role in the intricate regulation of gene expression. Its dysregulation is a frequent occurrence in the context of cancer. Hypomethylation events can lead to increased genomic instability and the aberrant activation of oncogenes, while conversely, hypermethylation of promoter regions often results in the silencing of crucial tumor suppressor genes. These epigenetic alterations are not random occurrences; rather, they frequently manifest in specific patterns that can serve as valuable diagnostic or prognostic indicators for cancer patients. Consequently, these patterns are actively being explored as potential therapeutic targets for effective cancer treatment[2].
Histone modifications, a diverse group of post-translational modifications including acetylation, methylation, phosphorylation, and ubiquitination, exert a profound impact on chromatin structure and gene accessibility. This influence directly affects cellular processes, thereby impacting oncogenesis. Dysregulation of the enzymes responsible for these histone modifications, such as histone deacetylases (HDACs) and histone methyltransferases (HMTs), is a common and significant feature observed across a wide spectrum of cancers. Such alterations can lead to aberrant gene expression patterns that actively promote cancer cell proliferation, enhance survival mechanisms, and facilitate metastasis, establishing them as attractive targets for the development of epigenetic therapies[3].
Non-coding RNAs (ncRNAs), a broad category encompassing microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), function as crucial regulators of gene expression and are increasingly acknowledged for their significant roles in cancer development. miRNAs can operate as either oncogenes or tumor suppressors by modulating the expression of target genes at the post-transcriptional level. LncRNAs, in turn, can interact with DNA, RNA, and proteins to modulate critical cellular processes such as chromatin structure, transcription, and post-transcriptional regulation. The aberrant expression of these ncRNAs in cancer is a contributing factor to various hallmarks of the disease, underscoring their importance in oncogenesis[4].
The epigenomic landscape is inherently dynamic, susceptible to influence from both intrinsic genetic factors and external environmental exposures. Within the context of cancer, these epigenetic changes are not static but evolve in concert with tumor progression. This evolution contributes to intra-tumor heterogeneity and is a significant factor in the development of drug resistance. Therapeutic interventions strategically designed to reprogram these aberrant epigenetic marks, such as the use of DNA methyltransferase inhibitors and histone deacetylase inhibitors, are demonstrating considerable promise in clinical settings, offering new hope for patient management[5].
Single-cell epigenomics is ushering in a revolutionary era in our understanding of cancer heterogeneity. By meticulously analyzing the epigenomic profiles of individual cells within a tumor, researchers are now capable of identifying distinct cell populations, tracking their developmental trajectories, and elucidating how epigenetic plasticity contributes to therapeutic resistance and disease relapse. This granular, high-resolution approach is absolutely crucial for dissecting the complexities of tumors and for formulating more effective, personalized therapeutic strategies tailored to the unique characteristics of each patient's cancer[6].
The intricate interplay between the genome and the epigenome is absolutely critical for maintaining cellular identity and effectively suppressing oncogenic transformation. Mutations occurring in genes that encode epigenetic regulators, such as the IDH1/2 or TET enzymes, can precipitate widespread epigenetic dysregulation, thereby driving cancer initiation and progression. A comprehensive understanding of these complex genetic-epigenetic interactions provides invaluable insights into the multifaceted molecular mechanisms that underlie the development of cancer, paving the way for targeted interventions[7].
Epigenetic biomarkers hold immense potential for revolutionizing cancer care, offering promising applications in early detection, accurate diagnosis, precise prognosis, and the prediction of treatment response. Specifically, DNA methylation patterns detected in circulating tumor DNA (ctDNA) are emerging as particularly promising candidates for non-invasive liquid biopsy approaches. Significant advancements in high-throughput sequencing technologies and sophisticated bioinformatics tools are now enabling the identification and rigorous validation of robust epigenetic signatures applicable to a wide array of cancer types, transforming diagnostic capabilities[8].
Epigenetic therapy represents a strategic approach aimed at reversing the aberrant epigenetic changes that occur in cancer cells, with the ultimate goal of restoring normal gene expression patterns. This therapeutic modality involves targeting the enzymes responsible for adding or removing epigenetic marks, including DNA methyltransferases and histone deacetylases. The exploration of combination therapies, which integrate epigenetic drugs with conventional chemotherapy, immunotherapy, or other targeted therapies, is a critical area of research focused on overcoming treatment resistance and significantly improving overall therapeutic efficacy[9].
The tumor microenvironment (TME) plays an indispensable role in the complex process of cancer development. Epigenetic mechanisms are increasingly being implicated in shaping the composition and functional characteristics of the TME. Cancer cells possess the ability to induce epigenetic changes in surrounding stromal cells, immune cells, and endothelial cells within the TME. These induced changes can significantly influence crucial processes such as immune evasion, angiogenesis, and metastasis. Therefore, a deep understanding of these epigenetic cross-talks within the TME is vital for the successful development of effective anti-cancer strategies[10].
Epigenomic alterations are recognized as fundamental drivers of cancer development, exerting their influence by modulating gene expression without altering the underlying DNA sequence. These modifications encompass DNA methylation, histone modifications, and non-coding RNAs, collectively forming the epigenomic landscape. Aberrant patterns in these epigenetic marks can lead to the silencing of tumor suppressor genes, the activation of oncogenes, and the promotion of genomic instability, ultimately contributing to tumor initiation, progression, and resistance to therapy. Understanding these dynamic changes provides promising avenues for novel diagnostic biomarkers and therapeutic strategies targeting epigenetic pathways[1].
DNA methylation, a pivotal epigenetic modification, plays a critical role in regulating gene expression and is frequently dysregulated in cancer. Hypomethylation can result in genomic instability and the activation of oncogenes, whereas hypermethylation of promoter regions often leads to the silencing of tumor suppressor genes. These alterations are not haphazard but often follow specific patterns that can serve as diagnostic or prognostic indicators and are actively being investigated as therapeutic targets for cancer treatment[2].
Histone modifications, including acetylation, methylation, phosphorylation, and ubiquitination, profoundly impact chromatin structure and gene accessibility, thereby influencing oncogenesis. The dysregulation of enzymes responsible for histone modifications, such as histone deacetylases (HDACs) and histone methyltransferases (HMTs), is a common characteristic in various cancers. These epigenetic alterations can result in aberrant gene expression patterns that promote cancer cell proliferation, survival, and metastasis, making them attractive targets for epigenetic therapies[3].
Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial regulators of gene expression and are increasingly acknowledged for their roles in cancer development. miRNAs can function as oncogenes or tumor suppressors by post-transcriptionally regulating target genes. LncRNAs can interact with DNA, RNA, and proteins to modulate chromatin structure, transcription, and post-transcriptional processes. Their aberrant expression in cancer contributes to various hallmarks of the disease[4].
The epigenomic landscape is highly dynamic and can be influenced by both intrinsic genetic factors and external environmental exposures. In cancer, these epigenetic changes are not static but evolve alongside tumor progression, contributing to heterogeneity and the development of drug resistance. Therapeutic interventions aimed at reprogramming these aberrant epigenetic marks, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, are showing promise in clinical settings[5].
Single-cell epigenomics is revolutionizing our understanding of cancer heterogeneity. By analyzing the epigenomic profiles of individual cells, researchers can identify distinct cell populations within a tumor, track their developmental trajectories, and understand how epigenetic plasticity contributes to resistance and relapse. This granular approach is crucial for dissecting complex tumors and developing more effective personalized therapies[6].
The interplay between the genome and epigenome is critical for maintaining cellular identity and suppressing oncogenic transformation. Mutations in genes encoding epigenetic regulators, such as IDH1/2 or TET enzymes, can lead to widespread epigenetic dysregulation, driving cancer initiation and progression. Understanding these genetic-epigenetic interactions provides insights into the complex molecular mechanisms underlying cancer development[7].
Epigenetic biomarkers hold immense potential for early cancer detection, diagnosis, prognosis, and predicting treatment response. DNA methylation patterns in circulating tumor DNA (ctDNA) are particularly promising for non-invasive liquid biopsies. Advances in high-throughput sequencing and bioinformatics are enabling the identification and validation of robust epigenetic signatures for various cancer types[8].
Epigenetic therapy aims to reverse aberrant epigenetic changes in cancer cells, restoring normal gene expression patterns. This involves targeting enzymes that add or remove epigenetic marks, such as DNA methyltransferases and histone deacetylases. Combination therapies, integrating epigenetic drugs with chemotherapy, immunotherapy, or targeted therapies, are being explored to overcome resistance and improve treatment efficacy[9].
The tumor microenvironment (TME) plays a crucial role in cancer development, and epigenetic mechanisms are increasingly implicated in shaping its composition and function. Cancer cells can induce epigenetic changes in stromal cells, immune cells, and endothelial cells within the TME, influencing immune evasion, angiogenesis, and metastasis. Understanding these epigenetic cross-talks within the TME is vital for developing effective anti-cancer strategies[10].
Epigenetic alterations are key drivers of cancer, impacting gene expression through mechanisms like DNA methylation, histone modifications, and non-coding RNAs. These changes can silence tumor suppressors, activate oncogenes, and promote instability, contributing to tumor initiation, progression, and treatment resistance. DNA methylation dysregulation, seen as hypomethylation or hypermethylation, plays a critical role in cancer. Histone modifications affect chromatin structure and gene accessibility, with their dysregulation common in cancers. Non-coding RNAs, including miRNAs and lncRNAs, are vital regulators involved in various cancer hallmarks. The epigenome is dynamic, influenced by genetics and environment, and evolves with tumor progression, impacting heterogeneity and drug resistance. Single-cell epigenomics offers detailed insights into cancer heterogeneity and resistance mechanisms. The interplay between the genome and epigenome is crucial for cellular identity and cancer suppression, with mutations in epigenetic regulators driving cancer. Epigenetic biomarkers show promise for early detection, diagnosis, and prognosis, especially DNA methylation in ctDNA. Epigenetic therapies target enzymes modifying epigenetic marks, aiming to reverse aberrant changes and improve treatment efficacy, often through combination therapies. The tumor microenvironment is also shaped by epigenetic mechanisms, influencing cancer development and progression.
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Journal of Genetics and DNA Research received 3 citations as per Google Scholar report
