ArticleThe EMBO journal2008
A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 1 of them a synthesis that pooled it.
What it found
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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
183 citing papers in PubMed, 1 synthesis or guideline pooled it, 323 citations in OpenAlex.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.Scientific reports · 2015Trial
- PARP inhibitor YCH1899 activates type I interferon signaling and synergizes with STING agonists in BRCA-proficient tumors.Molecular biomedicine · 2026Article
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Multicheckpoint Cellular Targeting of siRNAs Using Antibody-Directed Lipid-Polymer Hybrid Nanoparticles.Bioconjugate chemistry · 2025Article
- Targeting PARP1: A Promising Approach for Next-Generation Poly (ADP-ribose) Polymerase Inhibitors.Current breast cancer reports · 2025Review
- Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition.Nature cell biology · 2024Article
- Endogenous base damage as a driver of genomic instability in homologous recombination-deficient cancers.DNA repair · 2024Review
- Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Predicting host-based, synthetic lethal antiviral targets from omics data.NAR molecular medicine · 2024Article
- Advances in synthetic lethality modalities for glioblastoma multiforme.Open medicine (Warsaw, Poland) · 2024Review
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- Relevance of ATM Status in Driving Sensitivity to DNA Damage Response Inhibitors in Patient-Derived Xenograft Models.Cancers · 2023Article
- C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption.Nature communications · 2023Article
- Predicting host-based, synthetic lethal antiviral targets from omics data.bioRxiv : the preprint server for biology · 2023Article
- Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility.Nature communications · 2023Article
- Targeting ATR in Cancer Medicine.Cancer treatment and research · 2023Article
- Multiomics insights on the onset, progression, and metastatic evolution of breast cancer.Frontiers in oncology · 2023Review
- Molecular Biology Mechanisms and Emerging Therapeutics of Triple-Negative Breast Cancer.Biologics : targets & therapy · 2023Review
123 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibitors of poly (ADP-ribose)-polymerase-1 (PARP) are highly lethal to cells with deficiencies in BRCA1, BRCA2 or other components of the homologous recombination pathway. This has led to PARP inhibitors entering clinical trials as a potential therapy for cancer in carriers of BRCA1 and BRCA2 mutations. To discover new determinants of sensitivity to these drugs, we performed a PARP-inhibitor synthetic lethal short interfering RNA (siRNA) screen. We identified a number of kinases whose silencing strongly sensitised to PARP inhibitor, including cyclin-dependent kinase 5 (CDK5), MAPK12, PLK3, PNKP, STK22c and STK36. How CDK5 silencing mediates sensitivity was investigated. Previously, CDK5 has been suggested to be active only in a neuronal context, but here we show that CDK5 is required in non-neuronal cells for the DNA-damage response and, in particular, intra-S and G(2)/M cell-cycle checkpoints. These results highlight the potential of synthetic lethal siRNA screens with chemical inhibitors to define new determinants of sensitivity and potential therapeutic targets.
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.