Targeting cancer epigenetic pathways with small-molecule modulators for potential therapeutic purposes.

Epigenetic Targeting in Myeloid Malignancies.

Epigenetic mechanisms and clinical translation in ovarian cancer: from molecular pathways to precision therapy

Abstract Ovarian cancer remains one of the deadliest gynecological malignancies, mainly due to its late diagnosis, biological heterogeneity, and frequent development of chemoresistance. Recent evidence indicates that epigenetic dysregulation including aberrant DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA networks plays an important role in the initiation, progression, and therapeutic response of ovarian cancer. Unlike genetic alterations, epigenetic modifications are reversible, making them attractive targets for drug development and precision oncology. In this review, we provide a detailed overview of the epigenetic mechanisms that control ovarian cancer biology, with specific focus on their role in drug resistance and disease recurrence. We discuss the role of epigenetic plasticity in enabling transition of tumor cells into drug tolerant, stem like phenotypes, leading to minimal residual disease and eventual relapse without permanent genetic changes. Attention is given to the influence of DNA methyltransferases, histone deacetylases, enhancer of zeste homolog 2, and chromatin remodeling complexes in the maintenance of adaptive resistance programs. We also discuss the evolving paradigm of epigenetic regulation, immune modulation and viral mimicry and provide the rationale for combining epigenetic therapies with immunotherapy and poly(ADP-ribose) polymerase inhibition. The article also reviews the results of recent clinical trials and evaluate the most recent advances in biomarker development, such as circulating DNA methylation signatures, microRNAs, and artificial intelligence-based liquid biopsy platforms. Finally, we discussed the potential implications of applying epigenetic profiling in the clinic for improved patient stratification and the potential for real-time monitoring of chemoresistance. These progresses make epigenetic regulation a promising strategy to overcome chemoresistance and improve personalized medicine of ovarian cancer.

Nanotechnology-Based Strategies for Modulating Epigenetic Dysregulation in Cancer

Epigenetic dysregulation is a defining feature of cancer, driving malignant transformation, tumor progression, and therapeutic resistance through reversible yet heritable alterations in gene expression. Aberrant DNA methylation, histone modifications, and chromatin remodeling disrupt normal cellular identity and enable oncogenic transcriptional programs without altering the underlying DNA sequence. Although epigenetic enzymes are druggable and several epigenetic inhibitors have reached clinical use, their therapeutic impact has been constrained by limited specificity, systemic toxicity, poor pharmacokinetics, and the inability to precisely modulate complex epigenetic networks within tumors. Nanotechnology-based strategies have emerged as powerful tools to address these limitations by enabling targeted delivery, controlled release, and combinatorial modulation of epigenetic regulators. By leveraging nanoscale materials such as liposomes, polymeric nanoparticles, inorganic nanocarriers, and self-assembled systems, epigenetic drugs can be selectively delivered to tumor cells and subcellular compartments, enhancing efficacy while minimizing off-target effects. This review provides a comprehensive overview of nanotechnology-based approaches for modulating epigenetic dysregulation in cancer. We examine the biological basis of epigenetic alterations in malignancy, discuss major nanocarrier platforms for epigenetic therapy, and highlight advances in targeting DNA methylation, histone modifications, and chromatin architecture. Current challenges, translational considerations, and future directions for precision epigenetic nanomedicine are also critically discussed. Keywords: epigenetic therapy; nanotechnology; cancer; chromatin regulation; precision oncology.

Epigenetic modulators in triple-negative breast cancer: epigenetic modifications and future treatment perspectives.

Triple Negative Breast Cancer (TNBC), an aggressive type of Breast Cancer (BC) characterized by the loss of expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2) protein. TNBC is quite heterogenous in nature with limited available therapeutic options due to the lack of defined molecular targets. Epigenetic abnormalities have been implicated in the onset, progression, immune escape, and resistance to treatment in TNBC. Important epigenetic modulations, include DNA methylation, histone lactylation, histone modifications, and chromatin remodeling. Global hypomethylation contributes to genomic instability, while promoter hypermethylation inhibits tumor suppressor genes, by dysregulating their expression, thereby promoting uncontrolled proliferation, EMT, metastasis, and immune evasion in TNBC. Targeting epigenetic modulators, have the potential to develop novel therapeutic interventions have been developed and being explored. These epidrugs have proven to be effective in preclinical and clinical trials when used in combination with chemotherapy, immunotherapy, or targeted therapy, reducing drug resistance and aberrant proliferation. Despite of the advancements, challenges like target specificity, precise biomarkers and treatment related toxicity are the major hurdles. The review comprehensively summarized the important epigenetic alterations as well as novel treatment strategies with potential clinical applications in TNBC.

Nanotechnology-Driven Epigenetic Targeting: Tailoring Ovarian Cancer Therapeutics

Epigenetic mechanisms play a crucial role in OC drug resistance, and emerging evidence suggests that dysregulated epigenetic modifications are among the key contributors to OC. Epigenetic agents, including DNA methyltransferase inhibitors, histone deacetylase inhibitors, and non-coding RNA-based therapeutics, have important limitations, including poor water solubility, limited tissue distribution, low stability, and systemic toxicity. To overcome this, a novel drug delivery system is needed to manage variability in drug administration and maximize the efficacy of these drugs. In this regard, nanotechnology offers an attractive option for formulating epigenetic drugs with various encapsulation strategies to increase bioavailability and drug efficacy, reduce drug dose, administration frequency, and toxicity, and enhance cellular internalization and tumor-targeted delivery. In this review, we summarize various epigenetic regulators and their roles in OC therapy resistance as well as the development of nanosystems for epigenetic drug delivery, which could lay the foundation for designing nanoformulations encapsulating epigenetic therapeutics, ultimately advancing personalized, targeted therapy for patients with OC. This review also discusses the current clinical status of nanocarrier platforms and translational barriers that limit the clinical development of epigenetic nanomedicine, highlighting the future directions required for successful clinical translation.

Targeting DNA Methylation: New Paradigms and the Advent of Gene-Selective Tools.

The mechanisms and roles of DNA methylation in epigenetic regulation are examined, the current landscape of DNA methylation modulators are evaluated, from traditional DNMT inhibitors to cutting-edge CRISPR-dCas9 fusion systems and protein-protein interaction disruptors, and their clinical relevance are evaluated.