Abstract Drug resistance remains a major challenge in the treatment of ovarian cancer and is a leading cause of recurrence and poor clinical outcomes. Increasing evidence has identified acetylation as a critical epigenetic and post-translational modification that contributes to therapeutic resistance through the regulation of chromatin accessibility, gene transcription, protein function, and cellular signaling. Recent studies suggest that acetylation functions as an integrative regulatory hub linking multiple resistance-associated processes, including DNA damage repair, cancer stemness, cellular plasticity, metabolic adaptation, and immune evasion. In this review, we summarize the molecular mechanisms by which histone and non-histone acetylation, together with acetylation-associated regulatory networks, drive ovarian cancer drug resistance. We further discuss current advances in acetylation-targeted therapeutic strategies, including HDAC inhibitors, BET inhibitors, emerging KAT inhibitors, and rational combination approaches designed to overcome resistance. Collectively, acetylation-centered regulatory networks represent promising therapeutic targets in ovarian cancer. A deeper understanding of these mechanisms may facilitate biomarker-guided patient stratification and support the development of more effective strategies for overcoming drug resistance.
Chen et al. (Sat,) studied this question.