Evidence map›Paper›PMID 41475353›Full record

ArticleCell reports methods2026

Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor.

Daniel Marks, Edwin Garcia, Sunil Kumar, Katie Tyson, Caroline Koch, Aleksandar P Ivanov, Joshua B Edel, Hasan B Mirza, William Flanagan, Christopher Dunsby and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Daniel MarksOvarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK; Francis Crick Institute, London NW1 1AT, UK; Department of Physics, Imperial College London, London SW7 2AZ, UK.
Edwin GarciaOvarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK; Francis Crick Institute, London NW1 1AT, UK; Department of Physics, Imperial College London, London SW7 2AZ, UK.
Sunil KumarFrancis Crick Institute, London NW1 1AT, UK; Department of Physics, Imperial College London, London SW7 2AZ, UK.
Katie TysonOvarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK.
Caroline KochDepartment of Chemistry, Imperial College London, London W12 0BZ, UK.
Aleksandar P IvanovDepartment of Chemistry, Imperial College London, London W12 0BZ, UK.
Joshua B EdelDepartment of Chemistry, Imperial College London, London W12 0BZ, UK.
Hasan B MirzaOvarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK.
William FlanaganFrancis Crick Institute, London NW1 1AT, UK; Department of Physics, Imperial College London, London SW7 2AZ, UK.
Christopher DunsbyFrancis Crick Institute, London NW1 1AT, UK; Department of Physics, Imperial College London, London SW7 2AZ, UK.
Paul M W FrenchFrancis Crick Institute, London NW1 1AT, UK; Department of Physics, Imperial College London, London SW7 2AZ, UK.
Iain A McNeishOvarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0NN, UK. Electronic address: i.mcneish@imperial.ac.uk.

Funding

Wellcome Trust FC001999
6 · The paper itself

Abstract

Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian high-grade serous carcinoma (HGSC), particularly in homologous recombination-deficient tumors. However, the emergence of resistance poses a critical challenge, as over 50% of patients relapse within 3 years. The mechanisms underlying changes in PARP trapping, a central aspect of PARPi efficacy, are not well understood, as current experimental methodologies lack resolution and throughput. To address this, we develop an intramolecular fluorescence resonance energy transfer (FRET)-based biosensor by CRISPR-Cas9 dual labeling of endogenous PARP1 with EGFP and mCherryFP in OVCAR4 cells. This biosensor enables real-time, single-cell analysis of PARP trapping dynamics. Using fluorescence lifetime imaging microscopy (FLIM), we reveal dose-dependent PARP trapping, differentiate the trapping efficiencies of four clinically approved PARPi, and observe reduced trapping in PARPi-resistant models in vitro and in vivo. This biosensor provides critical insights into PARPi resistance mechanisms, with implications for developing more effective therapies and advancing personalized treatment for ovarian cancer patients.

Indexed as

Biosensing TechniquesCRISPR-Cas SystemsFluorescence Resonance Energy TransferOvarian NeoplasmsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesAnimalsCell Line, TumorFemaleHumansMicePoly(ADP-ribose) Polymerase InhibitorsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesCP: imagingDNA damageFLIM-FRET imagingovarian cancerPARP1PARP inhibitorPARP trapping

Identifiers

PMID41475353
PMCPMC12853179

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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.