20.500.12556/RUL-166742 Targeting estrogen metabolism in high-grade serous ovarian cancer shows promise to overcome platinum resistance The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need to determine optimal treatment strategies for advanced and recurrent cases. Our study investigates the interplay between estrogens and chemoresistance in HGSOC and shows clear differences between platinum-sensitive and -resistant tumors. Through comprehensive transcriptome analyzes, we uncover differences in the expression of genes of estrogen biosynthesis, metabolism, transport and action underlying platinum resistance in different tissues of HGSOC subtypes and in six HGSOC cell lines. Furthermore, we identify genes involved in estrogen biosynthesis and metabolism as prognostic biomarkers for HGSOC. Additionally, our study elucidates different patterns of estrogen formation/metabolism and their effects on cell proliferation between six HGSOC cell lines with different platinum sensitivity. These results emphasize the dynamic interplay between estrogens and HGSOC chemoresistance. In particular, targeting the activity of steroid sulfatase (STS) proves to be a promising therapeutic approach with potential efficacy in limiting estrogen-driven cell proliferation. Our study reveals potential prognostic markers as well as identifies novel therapeutic targets that show promise for overcoming resistance and improving treatment outcomes in HGSOC. high-grade serous ovarian cancer estrogen metabolisem prognostic biomarkers therapeutic targets transcriptomic analysis chemoresistance serozni rak jajčnikov visoke stopnje metabolizem estrogena prognostični biomarkerji terapevtske tarče transkriptomska analiza true false true Angleški jezik Slovenski jezik Članek v reviji 2025-01-23 14:13:03 2025-01-23 14:13:07 2025-01-24 04:05:30 0000-00-00 00:00:00 2024 0 0 17 str. Vol. 177, art. 117069 Aug. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.2 1950-6007 10.1016/j.biopha.2024.117069 202256387 1-s2.0-S0753332224009533-main.pdf 1-s2.0-S0753332224009533-main.pdf 1 6AB0EFCF6CE9640E85B4636508CBA1C3 bc595308cceb747b6b2415c46a28a36ddee0e1608c1f2ad9877700dbc870cad3 a001896c-d98b-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=198584 https://www.sciencedirect.com/science/article/pii/S0753332224009533 0 feb9e290-d98a-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=198582 Medicinska fakulteta 0 0 0