IRE1α Inhibitor Reduces Cisplatin Resistance in Ovarian Cancer by Modulating IRE1α/XBP1 Pathway

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2024 Nov 20

PMID 39565508

Authors

Shiyi Lv

Lin Zhang

Min Wu

Shuangshuang Zhu

Yixue Wang

Layang Liu

Yunxuan Li

Ting Zhang

Yujie Wu

Huang Chen

Mingyao Liu

Zhengfang Yi

Affiliations

Soon will be listed here.

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.

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