Evidence map›Paper›PMID 40391780›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Targeting GPX4 to Induce Ferroptosis Overcomes Chemoresistance Mediated by the PAX8-AS1/GPX4 Axis in Intrahepatic Cholangiocarcinoma.

Zhi-Wen Chen, Ji-Jun Shan, Mo Chen, Zong Wu, Yi-Ming Zhao, Hong-Xu Zhu, Xin Jin, Yi-Xiu Wang, Yi-Bin Wu, Zhen Xiang and 4 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Zhi-Wen ChenDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.ORCID https://orcid.org/0000-0002-1770-6208
Ji-Jun ShanDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Mo ChenDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Zong WuDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Yi-Ming ZhaoDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Hong-Xu ZhuDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Xin JinDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Yi-Xiu WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Yi-Bin WuDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Zhen XiangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Zhi-Wen DingDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Zhen-Hai LinDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Long-Rong WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Lu WangDepartment of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.ORCID https://orcid.org/0000-0002-6856-7084

Funding

Beijing iGandan Foundation GDXZ-08-02Beijing iGandan Foundation GDXZ-08-14Beijing iGandan Foundation HYXH202042Beijing iGandan Foundation HYXH2021074Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province CXPJJH124001-2474Key Project of Xuhui District Municipal Health Commission XHLHGG202103National Natural Science Foundation of China 81874182National Natural Science Foundation of China 82472956National Natural Science Foundation of China M-0334Shanghai Anti-cancer Association's Aoxiang Project SACA-AX202211Shanghai Xuhui District Hospital Local Cooperation Project 23XHYD-20
6 · The paper itself

Abstract

The standard regimen of gemcitabine combined with cisplatin offers limited clinical benefits in the treatment of advanced intrahepatic cholangiocarcinoma (ICC) due to intrinsic or acquired resistance. Currently, effective biomarkers to predict and improve chemotherapy resistance in ICC are lacking. Here, it is reported that a long non-coding RNA (lncRNA), PAX8-AS1, reduces the efficacy of standard chemotherapeutic drugs. Mechanistically, PAX8-AS1 activates NRF2 by binding to p62, thereby promoting GPX4 transcription, and stabilizes GPX4 mRNA through interaction with IGF2BP3. The PAX8-AS1/GPX4 axis inhibits ferroptosis and promotes resistance to gemcitabine and cisplatin. In preclinical models, the combination of the GPX4 inhibitor JKE-1674 with gemcitabine and cisplatin exhibits superior antitumor efficacy. These findings suggest a promising therapeutic strategy to improve chemotherapy efficacy in advanced ICC.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaDrug Resistance, NeoplasmFerroptosisPAX8 Transcription FactorPhospholipid Hydroperoxide Glutathione PeroxidaseRNA, Long NoncodingAnimalsCell Line, TumorCisplatinDeoxycytidineGemcitabineGene Expression Regulation, NeoplasticHumansMiceCisplatinDeoxycytidineGemcitabinePAX8 protein, humanPAX8 Transcription FactorPhospholipid Hydroperoxide Glutathione PeroxidaseRNA, Long NoncodingchemoresistanceferroptosisGPX4intrahepatic cholangiocarcinomaPAX8‐AS1

Identifiers

PMID40391780
PMCPMC12376697

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.