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@article{McNeish:2025,
author = {McNeish, I and Marks, D and Kumar, S and Tyson, K and Koch, C and Ivanov, A and Edel, J and Mirza, H and flanagan, W and Dunsby, C and French, P},
journal = {Cell Reports: Methods},
title = {Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor},
year = {2025}
}

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TY  - JOUR
AB  - SUMMARY 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 three 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 developed an intramolecular FRET-based biosensor by CRISPR-Cas9 dual-labelling 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 revealed dose-dependent PARP trapping, differentiated the trapping efficiencies of four clinically approved PARPi and observed 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.
AU  - McNeish,I
AU  - Marks,D
AU  - Kumar,S
AU  - Tyson,K
AU  - Koch,C
AU  - Ivanov,A
AU  - Edel,J
AU  - Mirza,H
AU  - flanagan,W
AU  - Dunsby,C
AU  - French,P
PY  - 2025///
SN  - 2667-2375
TI  - Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor
T2  - Cell Reports: Methods
ER  -

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