Epigenetic therapies in cancer treatment: Opportunities and challenges

Epigenetic therapies offer a revolutionary approach to cancer treatment by targeting reversible modifications such as DNA methylation, histone modifications, and non-coding RNAs that regulate gene expression. FDA-approved drugs like DNA methyltransferase inhibitors and histone deacetylase inhibitors have demonstrated clinical efficacy, particularly in hematologic malignancies, while emerging agents like BET and EZH2 inhibitors show promise in addressing therapeutic gaps in solid tumors. This review delves into these advancements, highlighting the integration of epigenetic drugs with immunotherapy, chemotherapy, and targeted therapies to enhance therapeutic precision and overcome resistance. Moreover, it emphasizes opportunities such as biomarker-driven personalization and liquid biopsy technologies for real-time monitoring, alongside innovations like single-cell epigenomics and CRISPR-based tools that facilitate tumor heterogeneity studies and precise therapeutic interventions. Despite these developments, challenges such as off-target effects, delivery inefficiencies, and regulatory hurdles persist, necessitating further innovation. By integrating epigenetic therapies with RNA-based drugs, nanomedicine, personalized vaccines, 3D epigenomics, and artificial intelligence, this review underscores the transformative potential of these therapies in redefining oncology, offering personalized, durable, and precise solutions to the complexities of cancer.