Evidence map›Paper›PMID 41172995›Full record

ArticleCell reports. Medicine2025

Co-targeting CDK4/6 enhances anti-cancer activity and alleviates immune-related adverse events of anti-PD-1 antibody for breast cancer.

Shu-Wei Hu, Ming-Hsin Yeh, Yu-Hao He, Ya-Ling Wei, Fang-Ju Cheng, Yi-Lun Yeh, Thanh Kieu Huynh, Pei-Tong Liu, Dai-Wei Hu, Tzu-Hsuan Chang and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. 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

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

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

20 authors.

Shu-Wei HuGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Ming-Hsin YehDepartment of Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Yu-Hao HeCenter for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung 407, Taiwan.
Ya-Ling WeiGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Fang-Ju ChengCenter for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Yi-Lun YehGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Thanh Kieu HuynhGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Pei-Tong LiuCenter for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Dai-Wei HuGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Tzu-Hsuan ChangDepartment of Fundamental Oncology, University of Lausanne, 1015 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1015 Lausanne, Switzerland.
Bo-Wei WangGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan.
Bo-Rong ChenGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan; School of Medicine, China Medical University, Taichung 404, Taiwan.
Mei-Chun LinDepartment of Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Der-Yen LeeInstitute of Integrated Medicine, China Medical University, Taichung 404, Taiwan.
Yi-Hsien HsiehInstitute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Yuan-Man HsuDepartment of Animal Science and Biotechnology, Tunghai University, Taichung 407, Taiwan.
Chih-Hsin TangGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; School of Medicine, China Medical University, Taichung 404, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan; Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan.
Ping-Chih HoDepartment of Fundamental Oncology, University of Lausanne, 1015 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1015 Lausanne, Switzerland.
Mien-Chie HungGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung 407, Taiwan; Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan.
Wei-Chien HuangGraduate Institute of Biomedical Sciences, China Medical University, Taichung 407, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 407, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung 407, Taiwan; Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu 302, Taiwan; Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan. Electronic address: whuang@mail.cmu.edu.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Early-onset breast cancer (EOBC) increases annually with unclear mechanisms and shows poor therapeutic responses and survival rates. We identify environmental exposure to the common plasticizer di-2-ethylhexyl phthalate (DEHP) as a contributing factor to breast tumor initiation by impairing cancer immune surveillance. DEHP exposure upregulates the immune checkpoint molecule programmed death-ligand 1 (PD-L1) through estrogen receptor beta (ERβ) activation in human breast cancer cells and mouse models. Transcriptomic analysis reveals cyclin-dependent kinase 4 (CDK4) as a key mediator of DEHP-induced immunosuppressive signaling. The CDK4/6 inhibitor palbociclib suppresses ERβ, programmed cell death protein 1 (PD-1), and PD-L1 expression, enhances anti-tumor responses, and reduces immune-related adverse events caused by anti-PD-1 antibody treatment in mice. While the strongest immune alterations appear in DEHP-exposed EOBC patients, the mechanisms extend to DEHP-associated breast cancer regardless of age. This study highlights immune dysregulation as a hallmark of DEHP-related breast carcinogenesis and supports co-targeting CDK4/6 and PD-L1 as a therapeutic strategy.

Indexed as

Breast NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Programmed Cell Death 1 ReceptorAnimalsB7-H1 AntigenCell Line, TumorDiethylhexyl PhthalateEstrogen Receptor betaFemaleHumansMicePiperazinesPyridinesB7-H1 AntigenCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Diethylhexyl PhthalateEstrogen Receptor betapalbociclibPiperazinesProgrammed Cell Death 1 ReceptorPyridinesCDK4 inhibitorearly-onset breast cancerendocrine disruptorERβestrogen receptor betaimmune checkpointimmune-related adverse eventsirAEsPD-1PD-L1plasticizertumor microenvironment

Identifiers

PMID41172995
PMCPMC12711678

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.