Fig. 5

Epigenetic modification. Epigenetic processes regulate gene expression through DNA methylation, histone modification, and non-coding RNA (ncRNAs) without altered DNA sequences. Hypermethylation of ABCB1 and demethylation of ABCG2 promoter lead to chemoresistance in ovarian cancer. The loss of RAD51C promoter methylation and the downregulation of BRCA1 methylation have been verified to cause drug resistance. The specific H3K27 methyltransferase EZH2 confers chemoresistance on ovarian cancer cells through H3K27 methylation. A subclass of miRNAs, “epi-miRNAs”, can modulate epigenetic regulators to impact therapeutic responses. miR-152 and miR-185 co-contribute to the cisplatin resistance by directly targeting DNMT1, miR-15a and miR-16 directly target the Bmi-1 (a member of Polycomb complexes). They may serve as potential epigenetic therapeutic targets. Epigenetic therapy including DNMTi and HDACi can increase the number of CD45 + immune cells, active CD8 + T and NK cells in TME, reducing immunosuppression. Thus, the epigenetic therapy combined with immunotherapy may be a promising therapeutic strategy for resistant OC. (HDACs, histone deacetylases; H3K27, histone H3 lysine 27; EZH2, enhancer of zeste homolog 2; DNMTis, DNA methyltransferase inhibitors; HDACis, histone deacetylase inhibitors; Bmi-1: a member of Polycomb complexes)