Evidence map›Paper›PMID 38118413›Full record

ArticleCell reports. Medicine2023

PRMT blockade induces defective DNA replication stress response and synergizes with PARP inhibition.

Yang Li, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Travis D Kerr, Deepa Bisht, Yalong Wang, Sharad Awasthi, Babita Kaundal, Siqi Wu and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2023. 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
3.8field-weighted citation impact, top 6% of its field
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, 25 citations in OpenAlex.

  1. Trial
  2. Review
  3. Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026
    Review
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  5. Review
  6. Article
  7. Review
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  9. Article
  10. Review
  11. Review
  12. Article
  13. Targeting c-Myc-p300-CARM1 complex induces ferroptosis and reduces CD8International journal of biological sciences · 2026
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

24 authors at 7 institutions in 1 country.

Yang LiDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lacey E DobroleckiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Christina SallasLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Xudong ZhangDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Travis D KerrCenter for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH, USA.
Deepa BishtDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yalong WangDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sharad AwasthiDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Babita KaundalDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Siqi WuDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Weiyi PengDepartment of Biology and Biochemistry, University of Houston, Houston, TX, USA.
Marc L MendilloDepartment of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Yiling LuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Collene R JeterDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guang PengDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jinsong LiuDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shannon N WestinDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael T LewisLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Jishnu DasCenter for Systems Immunology, Department of Immunology, and Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
S Stephen YiLivestrong Cancer Institutes, Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA; Interdisciplinary Life Sciences Graduate Programs (ILSGP), College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA; Oden Institute for Computational Engineering and Sciences (ICES), The University of Texas at Austin, Austin, TX, USA; Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA.
Mark T BedfordDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Daniel J McGrailCenter for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH, USA; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: mcgraid@ccf.org.
Nidhi SahniDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX, USA. Electronic address: nsahni@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USCleveland Clinic · USLivestrong Foundation · USNorthwestern University · USUniversity of Houston · USUniversity of Pittsburgh · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
Network-based Framework to Decode Novel Gain-of-Function Mutations and their Mechanistic Roles in General Human DiseasesR35GM133658 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI S. Stephen Yi · 2019 to 2026
$2.6M
Deciphering Functional Consequences of Specific and Combinatorial Mutations in Protein Interaction NetworksR35GM137836 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SAHNI, NIDHI · 2020 to 2023
$1.8M
Functional Proteomics by Reverse Phase Protein Array in CancerR50CA221675 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LU, YILING · 2017 to 2021
$726k
NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA125123NCI NIH HHS R50 CA221675NIGMS NIH HHS R35 GM133658NIGMS NIH HHS R35 GM137836
6 · The paper itself

Abstract

Multiple cancers exhibit aberrant protein arginine methylation by both type I arginine methyltransferases, predominately protein arginine methyltransferase 1 (PRMT1) and to a lesser extent PRMT4, and by type II PRMTs, predominately PRMT5. Here, we perform targeted proteomics following inhibition of PRMT1, PRMT4, and PRMT5 across 12 cancer cell lines. We find that inhibition of type I and II PRMTs suppresses phosphorylated and total ATR in cancer cells. Loss of ATR from PRMT inhibition results in defective DNA replication stress response activation, including from PARP inhibitors. Inhibition of type I and II PRMTs is synergistic with PARP inhibition regardless of homologous recombination function, but type I PRMT inhibition is more toxic to non-malignant cells. Finally, we demonstrate that the combination of PARP and PRMT5 inhibition improves survival in both BRCA-mutant and wild-type patient-derived xenografts without toxicity. Taken together, these results demonstrate that PRMT5 inhibition may be a well-tolerated approach to sensitize tumors to PARP inhibition.

Indexed as

NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsArginineCell LineDNA ReplicationHumansProtein-Arginine N-MethyltransferasesRepressor ProteinsArgininePoly(ADP-ribose) Polymerase InhibitorsPRMT1 protein, humanPRMT5 protein, humanProtein-Arginine N-MethyltransferasesRepressor Proteinsarginine methylationbreast cancerDNA replication stressovarian cancerPARP inhibitorsPRMT inhibitors

Identifiers

PMID38118413
PMCPMC10772459
OpenAlexW4389955916

What OpenQuestion 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 OpenQuestion graph.