Angiogenesis, the formation of new blood vessels from preexisting ones, is essential for normal development, wound healing, and tissue repair. However, dysregulated angiogenesis is implicated in various pathological conditions, including cancer, diabetic retinopathy, and atherosclerosis. Epigenetic modifications, including DNA methylation, histone modification, and noncoding RNAs (e.g., miRNAs), play a crucial role in regulating angiogenic gene expression without altering the underlying DNA sequence. These modifications tightly regulate the balance between pro-angiogenic and anti-angiogenic factors, thereby influencing endothelial cell proliferation, migration, and tube formation. In recent years, epigenetic drugs, such as DNA methyltransferase inhibitors (e.g., azacitidine, decitabine), histone deacetylase inhibitors (e.g., vorinostat, romidepsin), and BET inhibitors (e.g., JQ1), have emerged as promising therapeutic strategies for targeting abnormal angiogenesis. These agents modulate gene expression patterns, reactivating silenced tumor suppressor genes while downregulating pro-angiogenic signaling pathways. Additionally, miRNA modulators, such as MRG-110 and MRG-201, provide precise regulation of angiogenesis-related pathways, demonstrating significant therapeutic potential in preclinical models. This review underscores the intricate interplay between epigenetic regulation and angiogenesis, highlighting key mechanisms and therapeutic applications. Advancing our understanding of these processes will enable the development of more effective and targeted epigenetic therapies for angiogenesis-related diseases, paving the way for innovative clinical interventions.

Abstract Drug resistance in epithelial ovarian cancer is reportedly attributed to the existence of cancer stem cells, because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells. We screened an FDA-approved compound and clinical libraries, and found several small molecule drugs that target ovarian CSCs. These drugs decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. Since these drugs harbor target proteins, we investigated the expression of the target proteins in ovarian CSC and found the increased level of the protein expression and new therapeutic markers of ovarian CSCs. Downregulation of these genes reduced the stem-cell-like properties of ovarianCSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with chemo agents, synergistic ect was shown in inhibiting the viability and proliferation of ovarian CSCs. Our results suggested that these may be potential therapeutic drugs for preventing ovarian cancer recurrence. Citation Format: Dong Kyu Choi, Sang Hyun Min. Screening of novel therapeutic markers for ovarian cancer stem cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A021.