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IRE1α inhibitor reduces cisplatin resistance in ovarian cancer by modulating IRE1α/XBP1 pathway.

Authors :
Lv S
Zhang L
Wu M
Zhu S
Wang Y
Liu L
Li Y
Zhang T
Wu Y
Chen H
Liu M
Yi Z
Source :
Cellular oncology (Dordrecht, Netherlands) [Cell Oncol (Dordr)] 2024 Dec; Vol. 47 (6), pp. 2233-2246. Date of Electronic Publication: 2024 Nov 20.
Publication Year :
2024

Abstract

Ovarian cancer, a leading cause of gynecological cancer deaths globally, poses significant treatment challenges. Cisplatin (CDDP) is the first treatment choice for ovarian cancer and it is initially effective. However, 80% of ovarian cancer patients eventually relapse and develop resistance, resulting in chemotherapy failure. Therefore, finding new treatment combinations to overcome ovarian cancer resistance can provide a new tactic to improve the ovarian cancer patients' survival rate. We first identified activation of the Unfolded Protein Response (UPR) in CDDP-resistant ovarian cancer cells, implicating the IRE1α/XBP1 pathway in promoting resistance. Our findings demonstrate that inhibiting IRE1α signaling can re-sensitizes resistant cells to CDDP in vivo and in vitro, suggesting that IRE1α inhibitor used in conjunction with CDDP presumably could merge as a novel therapeutic strategy. Here, our research highlights the critical role of IRE1α signaling in mediating CDDP resistance, and paves the way for improved treatment options through combinatorial therapy.<br />Competing Interests: Declarations. Animal ethical: All animals mentioned in this article were purchased from the Animal Center of East China Normal University. Animal care and maintenance complied with the guidelines of the Animal Investigation Committee of the Institute of Biomedical Sciences, East China Normal University. Competing interests: The authors declare no competing interests.<br /> (© 2024. Springer Nature Switzerland AG.)

Details

Language :
English
ISSN :
2211-3436
Volume :
47
Issue :
6
Database :
MEDLINE
Journal :
Cellular oncology (Dordrecht, Netherlands)
Publication Type :
Academic Journal
Accession number :
39565508
Full Text :
https://doi.org/10.1007/s13402-024-01010-z