Evidence map›Paper›PMID 39939726›Full record

ArticleOncogene2025

PPP2R1A mutations cause ATR inhibitor sensitivity in ovarian clear cell carcinoma.

James Stewart, Dragomir B Krastev, Rachel Brough, Diana Zatreanu, Feifei Song, Joseph S Baxter, Sandhya Sridhar, Jessica Frankum, Asha Konde, William Yang and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025
    Review
  5. Article
  6. Review
  7. Silencing PPP2R1A inhibits the progression of gastric cancer cells.Journal of cancer research and clinical oncology · 2025
    Article
  8. 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

27 authors.

James StewartThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Dragomir B Krastev *The CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0003-4298-7272
Rachel Brough *The CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Diana ZatreanuThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Feifei SongThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Joseph S BaxterThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Sandhya SridharThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Jessica FrankumThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
Asha KondeThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.
William YangThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0002-6398-4508
Syed HaiderBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0001-6685-5480
John AlexanderBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.
Kai BetteridgeLight microscopy Facility, The Institute of Cancer Research, London, SW3 6JB, UK.
Aditi GulatiBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.
Ayoma D AttygalleGynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK and Division of Clinical Studies, Institute of Cancer Research, London, UK.
Katherine VroobelGynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK and Division of Clinical Studies, Institute of Cancer Research, London, UK.
Rachael NatrajanBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0002-9987-2946
Saira KhaliqueBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.
Theodoros I RoumeliotisFunctional Proteomics Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0002-3354-5643
Jyoti S ChoudharyFunctional Proteomics Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0003-0881-5477
Jason YeungThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0003-2415-4824
Andrew J WicksThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0002-9307-3262
Rebecca MarlowBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.
Susana BanerjeeGynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK and Division of Clinical Studies, Institute of Cancer Research, London, UK.
Stephen J PettittThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0003-3313-3857
Andrew N J TuttBreast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.ORCID http://orcid.org/0000-0001-8715-2901
Christopher J LordThe CRUK Gene Function Laboratory, The Institute of Cancer Research, London, SW3 6JB, UK. chris.lord@icr.ac.uk.ORCID http://orcid.org/0000-0002-3226-0515

Funding

Cancer Research UK (CRUK) DRCRPG-Nov21\100001
6 · The paper itself

Abstract

Identification of ARID1A/ATR synthetic lethality led to ATR inhibitor phase II trials in ovarian clear cell carcinoma (OCCC), a cancer of unmet need. Using multiple CRISPR-Cas9 mutagenesis and interference screens, we show that inactivation of protein phosphatase 2A (PP2A) subunits, including PPP2R1A, enhance ATRi sensitivity in ARID1A mutant OCCC. Analysis of a new OCCC cohort indicates that 52% possess oncogenic PPP2R1A p.R183 mutations and of these, one half possessed both ARID1A as well as PPP2R1A mutations. Using CRISPR-prime editing to generate new isogenic models of PPP2R1A mutant OCCC, we found that PPP2R1A p.R183W and p.R183P mutations cause ATRi-induced S phase stress, premature mitotic entry, genomic instability and ATRi sensitivity in OCCC tumour cells. p.R183 mutation also enhanced both in vitro and in vivo ATRi sensitivity in preclinical models of ARID1A mutant OCCC. These results argue for the assessment of PPP2R1A mutations as a biomarker of ATRi sensitivity.

Indexed as

Adenocarcinoma, Clear CellAtaxia Telangiectasia Mutated ProteinsMutationOvarian NeoplasmsProtein Phosphatase 2AnimalsCell Line, TumorCRISPR-Cas SystemsDNA-Binding ProteinsDrug Resistance, NeoplasmFemaleHumansMiceTranscription FactorsXenograft Model Antitumor AssaysARID1A protein, humanAtaxia Telangiectasia Mutated ProteinsATR protein, humanDNA-Binding ProteinsPPP2R1A protein, humanProtein Phosphatase 2Transcription Factors

Identifiers

PMID39939726
PMCPMC11850283

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.