ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting Replication Fork Processing Synergizes with PARP Inhibition to Potentiate Lethality in Homologous Recombination Proficient Ovarian Cancers.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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.
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.
Who cites it
5 citing papers in PubMed.
- Acetylation in ovarian cancer: mechanistic insights into drug resistance and emerging therapeutic opportunities.Journal of ovarian research · 2026Review
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- PARP inhibitors and breast cancer: from therapeutic breakthrough to resistance challenge.Experimental & molecular medicine · 2026Review
- Targeting Replication Fork Processing Synergizes with PARP Inhibition to Potentiate Lethality in Homologous Recombination Proficient Ovarian Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Synthetic lethality in homologous recombination (HR)-deficient cancers caused by Poly (ADP-ribose) polymerase inhibitors (PARPi) has been classically attributed to its role in DNA repair. The mode of action of PARPi and resistance thereof are now believed to be predominantly replication associated. Therefore, effective combinatorial approaches of targeting replication fork processing along with HR-downregulation to target HR-proficient and possibly PARPi-resistant tumors are warranted. Stilbenes are a privileged class of molecules, which include resveratrol, pterostilbene, piceatannol, etc, that modulate both replication processes and RAD51-expression. In this investigation, by screening a small library of stilbenes, including in-house synthesized molecules, trans-4,4'-dihydroxystilbene (DHS) was discovered as a potent natural agent, which downregulates RAD51 expression and HR repair (GFP-reporter assay). DHS induces extensive synergistic cell death in ovarian cancers when combined with talazoparib (PARPi). Mechanistically, DHS elicits replication-stress through severely impeding replication fork progress, speed, and inducing fork-asymmetry. This leads to robust induction of single stranded DNA (ssDNA) gaps and poly-ADP-ribosylation (PARylation) in S-phase cells, signifying issues related to lagging (Okazaki) strand synthesis. PARPi, which abrogates PARylation, potentiates DHS induced ssDNA gaps, and their conversion into lethal double strand breaks through MRE11 action. Furthermore, the combination is highly effective in mitigating ovarian tumor xenograft growth in SCID mice and exhibited a good therapeutic-index with no/minimal tissue-toxicity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.