Epigenetic mechanisms and therapeutic advances in breast cancer: From molecular insights to clinical applications.

Abstract

Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality in women globally. While genetic mutations are well-established contributors to breast cancer pathogenesis, accumulating evidence underscores the pivotal role of epigenetic dysregulation including DNA methylation, histone modifications, and non-coding RNAs in driving tumor initiation, progression, metastasis, and therapeutic resistance. These reversible modifications regulate gene expression and chromatin structure without altering the underlying DNA sequence, offering unique opportunities for biomarker discovery and targeted intervention. This review provides a comprehensive overview of the epigenetic landscape in breast cancer, highlighting key molecular players such as BRCA1, RASSF1A, CDH1, and SOX17, and detailing the roles of histone acetylation, methylation, and phosphorylation in chromatin remodeling and gene regulation. The contributions of microRNAs and long non-coding RNAs in modulating cancer phenotypes and therapy responses are also discussed. Furthermore, we explore emerging epigenetic therapies ("epidrugs"), their integration with standard chemotherapy and immunotherapy, and the potential of multi-omics approaches in precision oncology. By linking molecular insights to clinical applications, this review emphasizes the promise of epigenetic strategies in advancing personalized treatment for breast cancer patients.