Evidence map›Paper›PMID 41795017›Full record

ArticleNPJ precision oncology2026

CDK4/6i reverse PARPi resistance by targeting the E2F1- MCM2/5 pathway.

Yujie Feng, Miao Fu, Bowen Zheng, Fanzhuoran Lou, Xintian Huang, Xiaowen Xie, Weijuan Tan, Quan Chen, Wenqing Zhang, Yongxiang Hong and 4 more

Abstract read
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In one paragraph

Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Yujie Feng *Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Miao Fu *Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Bowen Zheng *Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Fanzhuoran Lou *Department of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Xintian HuangDepartment of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Xiaowen XieXiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Weijuan TanDepartment of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Quan ChenDepartment of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Wenqing ZhangXiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Yongxiang HongDepartment of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Kaiyi RongDepartment of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Huibo ShiInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jimshihuibo@163.com.
Tianhui HuXiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China. thu@xmu.edu.cn.
Li XiaoDepartment of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China. xlshb0826@xmu.edu.cn.

Funding

Medical Innovation Project of Fujian Provincial Health Commission 2023CXB006Natural Science Foundation of Fujian Province 20247011335Shenzhen Science and Technology Program JCYJ20210324121802008, JCY20220530143406015the Open Research Project of the Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases (Ministry of Education), Gannan Medical University XN202005the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory 2023XAKJ0101005Xiamen Natural Science Foundation Project 3502Z20227266
6 · The paper itself

Abstract

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPis) like niraparib represents a major therapeutic challenge in ovarian cancer (OC). This study elucidates a novel resistance mechanism driven by the minichromosome maintenance proteins 2 and 5 (MCM2/5). In niraparib-resistant (NirR) OC cells, RNA-seq revealed upregulation of MCM2 and MCM5, which was functionally linked to enhanced proliferation and homologous recombination repair. Co-immunoprecipitation confirmed strengthened MCM2/5 interaction in NirR cells. Genetic knockdown of MCM2/5 resensitized NirR cells to niraparib, while their overexpression conferred resistance in parental cells. Mechanistically, the upregulation of MCM2/5 was transcriptionally regulated by the E2F1 transcription factor, activated via the CDK4/6-RB pathway. Consequently, pharmacological inhibition of CDK4/6 downregulated MCM2/5 expression and, when combined with niraparib, synergistically suppressed NirR tumor growth both in vitro and in vivo. Our findings identify the MCM2/5 complex as a critical mediator of PARPi resistance and establish the therapeutic potential of combining PARPis with CDK4/6 inhibitors to overcome this resistance in ovarian cancer.

Identifiers

PMID41795017
PMCPMC13096233

What Socratic holds

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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.