Evidence map›Paper›PMID 41191919›Full record

ArticleProtein & cell2026

Genome-wide CRISPR-Cas9 screening identifies CLK1 inhibition as a strategy to restore PARP inhibitor sensitivity via ERCC1 isoform switching.

Chaohua Liu, Fei Xu, Yutuan Wu, Jiana Li, Mengdong Ni, Siyu Xia, Lihua Chen, Haiyun Zhao, Min Yu, Yuqi Zhou and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein & cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

16 authors.

Chaohua LiuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Fei XuDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Yutuan WuDepartment of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310024, China.
Jiana LiDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Mengdong NiDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Siyu XiaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Lihua ChenDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Haiyun ZhaoDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Min YuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Yuqi ZhouDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Meiqin ZhangDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Jiajia LiDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Xiaohua WuDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Yan HuangDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Tao ZhuDepartment of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310024, China.
Xiaojun ChenDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Funding

Chinese Anti-Cancer Association-Hengrui PARP Inhibitor Cancer Research Fund CORP-252-1National Natural Science Foundation of China 82272682National Natural Science Foundation of China 82272898National Natural Science Foundation of China 82303660National Natural Science Foundation of China 82403208National Natural Science Foundation of China 82503636Noncommunicable Chronic Diseases-National Science and Technology Major 2025ZD0545600Science and Technology Commission of Shanghai Municipality 16411950200Science and Technology Commission of Shanghai Municipality 17411963000Science and Technology Commission of Shanghai Municipality 22YF1408100Science and Technology Commission of Shanghai Municipality 22YF1409100Science and Technology Commission of Shanghai Municipality KW1711Shanghai Anti-Cancer Association SACA-AX202215Social Development Project of Public Welfare Technology Research in Zhejiang Province LGF21H160008
6 · The paper itself

Abstract

Epithelial ovarian cancer (EOC) is an aggressive malignancy with limited therapeutic options. Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown remarkable efficacy, especially in BRCA-mutant patients, and are approved as maintenance therapy to prevent recurrence after initial response to chemotherapy. However, the development of PARPi resistance poses a major clinical challenge. This study utilized a whole-genome CRISPR-Cas9 genetic screening to identify genes associated with PARPi sensitivity upon knockout. Based on the screening and validated through further experiments, we confirmed that CLK1 knockdown is synthetically lethal with PARPi in ovarian cancer. The combination of the PARPi Olaparib and CLK1 inhibitor TG003 exhibited potent anti-proliferative effects both in vitro and in vivo. Mechanistically, CLK1 inhibition downregulated the functional ERCC1-202 isoform, resulting in enhanced DNA damage and apoptosis. Our findings reveal a novel mechanism underlying PARPi sensitivity and suggest that targeting CLK1 in combination with PARPi may represent a promising therapeutic strategy for PARPi-resistant ovarian cancer.

Indexed as

Carcinoma, Ovarian EpithelialCRISPR-Cas SystemsDNA-Binding ProteinsEndonucleasesOvarian NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesAnimalsApoptosisCell Line, TumorDrug Resistance, NeoplasmFemaleHumansMicePhthalazinesClk dual-specificity kinasesDNA-Binding ProteinsEndonucleasesERCC1 protein, humanolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProtein IsoformsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesCLK1CRISPR-Cas9 screenOvarian cancerPARP inhibitor

Identifiers

PMID41191919
PMCPMC12987568

What OpenQuestion holds

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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 OpenQuestion graph.