ArticleDNA repair2015
Alterations of DNA repair genes in the NCI-60 cell lines and their predictive value for anticancer drug activity.
Article in DNA repair, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis.Molecular cell · 2025Article
- Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs.Cancer discovery · 2024Article
- Mouse Slfn8 and Slfn9 genes complement human cells lacking SLFN11 during the replication stress response.Communications biology · 2023Article
- Reconsidering the mechanisms of action of PARP inhibitors based on clinical outcomes.Cancer science · 2022Review
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers.British journal of cancer · 2021Review
- Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells.Molecules (Basel, Switzerland) · 2021Article
- R-Loop-Mediated ssDNA Breaks Accumulate Following Short-Term Exposure to the HDAC Inhibitor Romidepsin.Molecular cancer research : MCR · 2021Article
- Functions of Thrombospondin-1 in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Advances in Small-Cell Lung Cancer (SCLC) Translational Research.Cold Spring Harbor perspectives in medicine · 2021Review
- SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells.Blood · 2021Article
- Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability.Frontiers in genetics · 2021Review
- Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.PloS one · 2021Article
- Chromatin Remodeling and Immediate Early Gene Activation by SLFN11 in Response to Replication Stress.Cell reports · 2020Article
- Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer.Exploration of targeted anti-tumor therapy · 2020Review
- Identification of pharmacodynamic biomarkers and common molecular mechanisms of response to genotoxic agents in cancer cell lines.Cancer chemotherapy and pharmacology · 2019Article
- DNA polymerase ζ in DNA replication and repair.Nucleic acids research · 2019Review
- Schlafen 11 (SLFN11), a restriction factor for replicative stress induced by DNA-targeting anti-cancer therapies.Pharmacology & therapeutics · 2019Review
- Schlafen 11 Restricts Flavivirus Replication.Journal of virology · 2019Article
- Tissue-Specific Chk1 Activation Determines Apoptosis by Regulating the Balance of p53 and p21.iScience · 2019Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Loss of function of DNA repair (DNAR) genes is associated with genomic instability and cancer predisposition; it also makes cancer cells reliant on a reduced set of DNAR pathways to resist DNA-targeted therapy, which remains the core of the anticancer armamentarium. Because the landscape of DNAR defects across numerous types of cancers and its relation with drug activity have not been systematically examined, we took advantage of the unique drug and genomic databases of the US National Cancer Institute cancer cell lines (the NCI-60) to characterize 260 DNAR genes with respect to deleterious mutations and expression down-regulation; 169 genes exhibited a total of 549 function-affecting alterations, with 39 of them scoring as putative knockouts across 31 cell lines. Those mutations were compared to tumor samples from 12 studies of The Cancer Genome Atlas (TCGA) and The Cancer Cell Line Encyclopedia (CCLE). Based on this compendium of alterations, we determined which DNAR genomic alterations predicted drug response for 20,195 compounds present in the NCI-60 drug database. Among 242 DNA damaging agents, 202 showed associations with at least one DNAR genomic signature. In addition to SLFN11, the Fanconi anemia-scaffolding gene SLX4 (FANCP/BTBD12) stood out among the genes most significantly related with DNA synthesis and topoisomerase inhibitors. Depletion and complementation experiments validated the causal relationship between SLX4 defects and sensitivity to raltitrexed and cytarabine in addition to camptothecin. Therefore, we propose new rational uses for existing anticancer drugs based on a comprehensive analysis of DNAR genomic parameters.
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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.