Epigenetics in Ovarian Cancer: A Review of Current Knowledge and Future Perspectives

Ovarian cancer is the gynecologic malignancy that bears the highest mortality rate in the Western world. This is attributed to late diagnosis and limited therapeutic progress. Recent advances in molecular oncology have highlighted the pivotal role of epigenetic modifications-including DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and RNA methylation-in ovarian cancer development, progression, and treatment resistance. DNA methylation patterns affect key tumor suppressors and oncogenes, while histone modifications alter chromatin accessibility, influencing gene expression. Chromatin remodeling complexes, particularly the SWI/SNF complex, are frequently mutated in specific ovarian cancer subtypes, which is central in shaping their biological behavior. Non-coding RNAs, including microRNAs and long non-coding RNAs, further regulate tumor cell behavior and the immunosuppressive tumor microenvironment. Epigenetic profiles vary among histological subtypes and hold promise for biomarker development, early detection, prognosis, and therapeutic monitoring. Liquid biopsy approaches leveraging circulating tumor DNA methylation show diagnostic potential superior to conventional markers. Moreover, targeting epigenetic regulators-such as DNMT and HDAC inhibitors, EZH2 antagonists, and RNA-modifying enzymes-offers novel avenues for treatment, particularly in reversing chemoresistance and sensitizing tumors to immunotherapy. While promising, these strategies require further validation through clinical research to translate into effective clinical interventions. This review aims to summarize the current literature and highlights potential applications of epigenetic manipulation in day-to-day practice.