Epigenetic regulation via histone modifications in ovarian cancer

Ovarian cancer is a highly heterogeneous and lethal gynecological malignancy, with its progression tightly regulated by both genetic and epigenetic mechanisms. Among the epigenetic regulators, histone modifications-including acetylation, methylation, phosphorylation, ubiquitination, and SUMOylation-have emerged as pivotal modulators of chromatin architecture and gene transcription. These post-translational modifications, governed by specific histone-modifying enzymes, shape the transcriptional landscape of tumor cells and influence key oncogenic processes such as cellular proliferation, invasion, stemness, DNA repair, and chemotherapy resistance. Dysregulation of enzymes such as histone acetyltransferases (HATs), deacetylases (HDACs), methyltransferases (HMTs), demethylases (HDMs), ubiquitin ligases, and SUMO ligases has been implicated in the pathogenesis of ovarian cancer and is associated with adverse clinical outcomes. Importantly, these modifications are reversible, rendering them tractable therapeutic targets. This review provides a comprehensive synthesis of the major classes of histone modifications and their biological functions in ovarian cancer, highlights recent insights into the interplay between different modifications (crosstalk), and evaluates ongoing therapeutic strategies that aim to reverse epigenetic dysregulation. By elucidating the complex epigenetic landscape, this review supports the development of next-generation diagnostic, prognostic, and therapeutic approaches in ovarian cancer.