Targeting estrogen metabolism in high-grade serous ovarian cancer shows promise to overcome platinum resistance.
Biomed Pharmacother
; 177: 117069, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38968802
ABSTRACT
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.
Key words
Carboplatin (PubChem CID: 10339178); Cisplatin (PubChem CID: 5460033); Estradiol (PubChem CID: 5757); Estradiol-3-sulfate (PubChem CID: 66416); Estrone (PubChem CID: 5870); Estrone-3-sulfate (PubChem CID: 20056857); High-grade serous ovarian cancer; STX64 (Irosustat) (PubChem CID: 5287541); chemoresistance; estrogen metabolism; prognostic biomarkers; therapeutic targets; transcriptomic analysis
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Drug Resistance, Neoplasm
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Cell Proliferation
/
Estrogens
Limits:
Female
/
Humans
Language:
En
Journal:
Biomed Pharmacother
Year:
2024
Document type:
Article
Country of publication: