Evidence map›Paper›PMID 35425960›Full record

ArticleCancer research2022

Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification.

Benedetta Pellegrino, Andrea Herencia-Ropero, Alba Llop-Guevara, Flaminia Pedretti, Alejandro Moles-Fernández, Cristina Viaplana, Guillermo Villacampa, Marta Guzmán, Olga Rodríguez, Judit Grueso and 29 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
8.8field-weighted citation impact, top 1% 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

68 citing papers in PubMed, 90 citations in OpenAlex.

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  19. International journal of oncology · 2025
    Review
  20. Assessing Determinants of Response to PARP Inhibition in GermlineInternational journal of molecular sciences · 2025
    Article

8 more citing papers are in PubMed but not listed here.

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

39 authors at 13 institutions in 8 countries.

Benedetta Pellegrino *Department of Medicine and Surgery, University of Parma, Italy.ORCID 0000-0001-9353-7445
Andrea Herencia-Ropero *Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Alba Llop-GuevaraExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Flaminia PedrettiExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Alejandro Moles-FernándezHereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Cristina ViaplanaOncology Data Science Group (ODysSey Group), Vall d'Hebron Institute of Oncology, Barcelona, Spain.ORCID 0000-0001-8904-4330
Guillermo VillacampaOncology Data Science Group (ODysSey Group), Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Marta GuzmánExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Olga RodríguezExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Judit GruesoExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Jose JiménezMolecular Oncology Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Enrique J ArenasGrowth Factors Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Andrea DegasperiAcademic Department of Medical Genetics, University of Cambridge, Addenbrooke's Treatment Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom.ORCID 0000-0001-6879-0596
João M L DiasAcademic Department of Medical Genetics, University of Cambridge, Addenbrooke's Treatment Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom.ORCID 0000-0002-8451-3537
Josep V FormentOncology iMED, AstraZeneca, Cambridge, United Kingdom.ORCID 0000-0002-7797-2583
Mark J O'ConnorDDR Biology Group, Bioscience, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.ORCID 0000-0003-1823-625X
Olivier DéasXenTech, Evry, France.
Stefano CairoXenTech, Evry, France.ORCID 0000-0002-4725-5970
Yinghui ZhouTESARO: A GSK company, Waltham, Massachusetts.
Antonino MusolinoDepartment of Medicine and Surgery, University of Parma, Italy.ORCID 0000-0002-7979-6261
Carlos CaldasCancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0003-3547-1489
Serena Nik-ZainalAcademic Department of Medical Genetics, University of Cambridge, Addenbrooke's Treatment Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Robert B ClarkeManchester Breast Centre, Division of Cancer Sciences, University of Manchester, Oglesby Cancer Research Building, Manchester, United Kingdom.ORCID 0000-0001-5407-3123
Paolo NuciforoMolecular Oncology Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.ORCID 0000-0003-1380-0990
Orland DíezHereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Xavier Serres-CréixamsDepartment of Radiology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.
Vicente PegPathology Department, Vall d'Hebron University Hospital, Barcelona, Spain.ORCID 0000-0002-5203-6166
Martín Espinosa-BravoBreast Surgical Unit, Breast Cancer Center, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.ORCID 0000-0002-4293-3875
Teresa MacarullaGastrointestinal and Endocrine Tumors Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Ana OakninDepartment of Medical Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.ORCID 0000-0002-3592-7194
Joaquin MateoDepartment of Medical Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.
Joaquín ArribasDepartment of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Barcelona, Spain.ORCID 0000-0002-0504-0664
Rodrigo DienstmannOncology Data Science Group (ODysSey Group), Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Meritxell BelletDepartment of Medical Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.ORCID 0000-0001-8859-8307
Mafalda OliveiraDepartment of Medical Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.ORCID 0000-0001-9152-8799
Cristina SauraDepartment of Medical Oncology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain.ORCID 0000-0001-8296-5065
Sara Gutiérrez-EnríquezHereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.ORCID 0000-0002-1711-6101
Judith BalmañaHereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.ORCID 0000-0002-0762-6415
Violeta SerraExperimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain.ORCID 0000-0001-6620-1065
Hebron University · PSVall d'Hebron Institut de Recerca · ESHutchison/MRC Research Centre · GBUniversitat Autònoma de Barcelona · ESUniversité d'Évry Val-d'Essonne · FRUniversity of Parma · ITVall d'Hebron Hospital Universitari · ESAstraZeneca (Singapore) · SGAstraZeneca (United Kingdom) · GBBreast Cancer Now · GBInstitució Catalana de Recerca i Estudis Avançats · ESTesaro (United States) · USUniversity of Cambridge · GB

Funding

TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
Cancer Research UK 16942Cancer Research UK 23916Cancer Research UK 29567Cancer Research UK A23916Cancer Research UK A25274Department of Health BRC-125-20014NCI NIH HHS P50 CA098131
6 · The paper itself

Abstract

PARP inhibitors (PARPi) are approved drugs for platinum-sensitive, high-grade serous ovarian cancer (HGSOC) and for breast, prostate, and pancreatic cancers (PaC) harboring genetic alterations impairing homologous recombination repair (HRR). Detection of nuclear RAD51 foci in tumor cells is a marker of HRR functionality, and we previously established a test to detect RAD51 nuclear foci. Here, we aimed to validate the RAD51 score cut off and compare the performance of this test to other HRR deficiency (HRD) detection methods. Laboratory models from BRCA1/BRCA2-associated breast cancer, HGSOC, and PaC were developed and evaluated for their response to PARPi and cisplatin. HRD in these models and patient samples was evaluated by DNA sequencing of HRR genes, genomic HRD tests, and RAD51 foci detection. We established patient-derived xenograft models from breast cancer (n = 103), HGSOC (n = 4), and PaC (n = 2) that recapitulated patient HRD status and treatment response. The RAD51 test showed higher accuracy than HRR gene mutations and genomic HRD analysis for predicting PARPi response (95%, 67%, and 71%, respectively). RAD51 detection captured dynamic changes in HRR status upon acquisition of PARPi resistance. The accuracy of the RAD51 test was similar to HRR gene mutations for predicting platinum response. The predefined RAD51 score cut off was validated, and the high predictive value of the RAD51 test in preclinical models was confirmed. These results collectively support pursuing clinical assessment of the RAD51 test in patient samples from randomized trials testing PARPi or platinum-based therapies. SIGNIFICANCE: This work demonstrates the high accuracy of a histopathology-based test based on the detection of RAD51 nuclear foci in predicting response to PARPi and cisplatin.

Indexed as

Breast NeoplasmsOvarian NeoplasmsCarcinoma, Ovarian EpithelialCisplatinFemaleHomologous RecombinationHumansPoly(ADP-ribose) Polymerase InhibitorsRad51 RecombinaseCisplatinPoly(ADP-ribose) Polymerase InhibitorsRAD51 protein, humanRad51 Recombinase

Identifiers

PMID35425960
PMCPMC7612637
OpenAlexW4223999681

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.