BibTex format
@article{Marks:2026:10.1016/j.crmeth.2025.101270,
author = {Marks, D and Garcia, E 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 and McNeish, I},
doi = {10.1016/j.crmeth.2025.101270},
journal = {Cell Reports: Methods},
title = {Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor},
url = {http://dx.doi.org/10.1016/j.crmeth.2025.101270},
volume = {6},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - SummaryPoly(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.
AU - Marks,D
AU - Garcia,E
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
AU - McNeish,I
DO - 10.1016/j.crmeth.2025.101270
PY - 2026///
SN - 2667-2375
TI - Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor
T2 - Cell Reports: Methods
UR - http://dx.doi.org/10.1016/j.crmeth.2025.101270
VL - 6
ER -