Targeting estrogen metabolism in high-grade serous ovarian cancer shows promise to overcome platinum resistance

Marolt, Nika (author), Pavlič, Renata (author), Kreft, Tinkara (author), Gjorgoska, Marija (author), Lanišnik-Rižner, Tea (author)

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.

• Language: English
• Keywords: high-grade serous ovarian cancer, estrogen metabolisem, prognostic biomarkers, therapeutic targets, transcriptomic analysis, chemoresistance
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 17 str.
• Numbering: Vol. 177, art. 117069
• PID: 20.500.12556/RUL-166742
• UDC: 577.2
• ISSN on article: 1950-6007
• DOI: 10.1016/j.biopha.2024.117069
• COBISS.SI-ID: 202256387
• Publication date in RUL: 23.01.2025

Record is a part of a journal

• Title: Biomedicine & pharmacotherapy
• Shortened title: Biomed. pharmacother.
• Publisher: Éditions scientifiques et médicales Elsevier
• ISSN: 1950-6007
• COBISS.SI-ID: 23136261

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: serozni rak jajčnikov visoke stopnje, metabolizem estrogena, prognostični biomarkerji, terapevtske tarče, transkriptomska analiza

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0449
• Name: Translacijska molekularna endokrinologija za zdravje žensk

• Funder: ARRS - Slovenian Research Agency
• Funding programme: Young researchers