AR/ERK co-targeting triggers ferroptosis via FOXC2 in triple-negative breast cancer

	AR/ERK co-targeting triggers ferroptosis via FOXC2 in triple-negative breast cancer
	Zhao, YH; Xu, C; Liu, YQ; Zhu, Y; Fan, LL; Gao, FY; Liang, XJ; Shi, YQ; Chen, YB; Guan, XX
	2026
发表期刊	Sci. China-Life Sci.
ISSN	1674-7305
卷号	69 期号:1 页码:85-100
摘要	Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, notably lacks effective treatment strategies. Although androgen receptor (AR) has emerged as a potential therapeutic target for TNBC, monotherapy with AR inhibitors has proven to be of restricted efficacy. Aiming to develop superior therapeutic approaches, a comprehensive drug library screening was conducted. The ERK inhibitor GDC-0994 exhibited significant synergistic effects with the AR inhibitor bicalutamide. Transcriptome sequencing showed that this combination therapy activates ferroptosis, as evidenced by elevated ROS, increased Fe2+ levels, a reduced GSH/GSSG ratio, and lipid peroxide accumulation (MDA and 4-HNE). FOXC2 was identified as a key mediator of this synergy. Specifically, the combination therapy inhibits FOXC2-driven EMT and induces ferroptosis via the FOXC2-Hippo signaling axis, suppressing tumor proliferation, migration, and invasion. In summary, this study uncovers the value of AR/ERK co-targeting in TNBC, which might potentiate the development of novel targeted therapeutic strategies in TNBC.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14912
专题	科研部门_肿瘤信号转导（陈勇彬）
推荐引用方式 GB/T 7714	Zhao, YH,Xu, C,Liu, YQ,et al. AR/ERK co-targeting triggers ferroptosis via FOXC2 in triple-negative breast cancer[J]. Sci. China-Life Sci.,2026,69(1):85-100.
APA	Zhao, YH.,Xu, C.,Liu, YQ.,Zhu, Y.,Fan, LL.,...&Guan, XX.(2026).AR/ERK co-targeting triggers ferroptosis via FOXC2 in triple-negative breast cancer.Sci. China-Life Sci.,69(1),85-100.
MLA	Zhao, YH,et al."AR/ERK co-targeting triggers ferroptosis via FOXC2 in triple-negative breast cancer".Sci. China-Life Sci. 69.1(2026):85-100.

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