Evidence map›Paper›PMID 40848720›Full record

ArticleCell reports. Medicine2025

Coordinated protein modules define DNA damage responses to carboplatin at single-cell resolution in human ovarian carcinoma models.

Jacob S Bedia, Antonio Delgado-Gonzalez, Ying-Wen Huang, Veronica D Gonzalez, Ionut-Gabriel Funingana, Zainab Rahil, Alyssa Mike, Alexis Lowber, Maria Vias, Alan Ashworth and 2 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. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jacob S BediaDepartment of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Antonio Delgado-GonzalezDepartment of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA; Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ying-Wen HuangDepartment of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Veronica D GonzalezBaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ionut-Gabriel FuninganaDepartment of Oncology, University of Cambridge, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Oncology, Cancer Services, Box 193, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Zainab RahilBaxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alyssa MikeDepartment of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alexis LowberDepartment of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Maria ViasCancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
Alan AshworthHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA.
James D BrentonDepartment of Oncology, University of Cambridge, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge CB2 0AH, UK; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Oncology, Cancer Services, Box 193, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
Wendy J FantlDepartment of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Comprehensive Cancer Institute, Stanford, CA 94305, USA; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: wjfantl@stanford.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tubo-ovarian high-grade serous carcinoma (HGSC), the most lethal gynecologic malignancy, initially responds to platinum-based chemotherapy, but due to frequent defects in the DNA damage response (DDR), most tumors develop resistance. The molecular mechanisms underlying clinical platinum resistance remain poorly defined with no biomarkers or targeted therapies to improve outcomes. Here, applying mass cytometry, we quantify phosphorylation and abundance of DDR proteins in carboplatin-treated HGSC cell line models. Despite similar levels of intranuclear platinum, a proxy for carboplatin uptake, cells follow divergent fates, reflecting DDR heterogeneity. Unsupervised analysis reveals a continuum of DDR states, and matrix factorization identifies eight protein modules. The activity of one module, containing canonical DDR proteins, increases in carboplatin-sensitive cells. Resistant cells engage a broader DDR protein module. These findings demonstrate the ability of single-cell proteomics to identify functional DDR states and reveal a DDR sensitivity module as a promising biomarker for clinical stratification and therapeutic decisions in HGSC.

Indexed as

CarboplatinDNA DamageOvarian NeoplasmsSingle-Cell AnalysisAntineoplastic AgentsCell Line, TumorDNA RepairDrug Resistance, NeoplasmFemaleHumansPhosphorylationProteomicsAntineoplastic AgentsCarboplatincarboplatin resistanceCIOV1CIOV2CIOV3DNA damage responsemass cytometry/CyTOFnon-negative matrix factorizationpartition-based graph abstractionsingle cellstubo-ovarian high grade carcinomaUniform ManifoldApproximation and Projection/UMAPUWB1.289

Identifiers

PMID40848720
PMCPMC12490248

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.