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@ARTICLE{Lin:298968,
author = {X. Lin and Y. Qiu and A. Soni and M. Stuschke$^*$ and G.
Iliakis},
title = {{R}eversing regulatory safeguards: {T}argeting the {ATR}
pathway to overcome {PARP} inhibitor resistance.},
journal = {Molecular therapy. Oncology.},
volume = {33},
number = {1},
address = {[New York]},
publisher = {Elsevier},
reportid = {DKFZ-2025-00397},
pages = {200934},
year = {2025},
note = {Molecular Therapy Oncology (Molecular Therapy Oncology) =
2950-3299 (import from CrossRef, PubMed, , Journals:
inrepo02.dkfz.de)},
abstract = {The development of poly (ADP-ribose) polymerase inhibitors
(PARPis) is widely considered a therapeutic milestone in the
management of BRCA1/2-deficient malignancies. Since a
growing number of cancer treatment guidelines include
PARPis, the inevitably emerging PARPi resistance becomes a
serious limitation that must be addressed. Targeting the DNA
damage response signaling kinase, ATR (ataxia telangiectasia
and rad3-related serine/threonine kinase), activated in
response to PARPi-induced replication stress, represents a
promising approach in fighting PARPi-resistant cancers. The
success of this combination therapy in preclinical models
has inspired efforts to translate its potential through
extensive clinical research and clinical trials. However,
the available clinical evidence suggests that PARPi/ATRi
combinations have yet to reach their anticipated therapeutic
potential. In this review, we summarize work elucidating
mechanisms underpinning the effectiveness of ATRi in
fighting PARPi resistance and review translational studies
reporting efficacy in different types of cancer. Finally, we
discuss potential biomarkers of patient selection for
customized combinations of PARPi/ATRi treatments.},
subtyp = {Review Article},
keywords = {ATR inhibitors (Other) / DNA double-stranded breaks (Other)
/ MT: Regular Issue (Other) / PARP inhibitors (Other) /
cancer (Other) / cell-cycle checkpoint (Other) /
chemotherapy (Other) / homologous recombination (Other) /
replication fork (Other)},
cin = {ED01},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39968096},
pmc = {pmc:PMC11834088},
doi = {10.1016/j.omton.2025.200934},
url = {https://inrepo02.dkfz.de/record/298968},
}