ArticleMolecular cancer therapeutics2014
Differential and common DNA repair pathways for topoisomerase I- and II-targeted drugs in a genetic DT40 repair cell screen panel.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 139 citations in OpenAlex.
- MPP8 Facilitates DNA DSB Repair via NHEJ to Promote Chemoresistance of TNBC Independent of Methyl-H3K9 Binding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor Payloads.Journal of molecular biology · 2026Review
- Targeted CRISPR knockout screening identifies known and novel chemogenomic interactions between DNA damaging agents and DNA repair genes.NAR cancer · 2026Article
- Prognostic model identification of ribosome biogenesis-related genes in pancreatic cancer based on multiple machine learning analyses.Discover oncology · 2025Article
- DNA Damage Response Pharmacogenomic (DDR_PGx) Score Predicts Response to Chemotherapy Consisting of Gemtuzumab Ozogamicin in Pediatric AML: A Report from the Children's Oncology Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- A BiInternational journal of nanomedicine · 2025Article
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- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- Inhibition of topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats.Nature communications · 2024Article
- The proofreading exonuclease of leading-strand DNA polymerase epsilon prevents replication fork collapse at broken template strands.Nucleic acids research · 2023Article
- Synthesis, DFT calculations, and anti-proliferative evaluation of pyrimidine and selenadiazolopyrimidine derivatives as dual Topoisomerase II and HSP90 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
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- Schlafen 11 (SLFN11) Kills Cancer Cells Undergoing Unscheduled Re-replication.Molecular cancer therapeutics · 2023Article
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- Discovery of novel DNA-damaging agents through phenotypic screening for DNA double-strand break.Cancer science · 2023Article
- Mechanisms of PARP Inhibitor Resistance.Cancer treatment and research · 2023Article
- Unboxing the molecular modalities of mutagens in cancer.Environmental science and pollution research international · 2022Review
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as tyrosyl-DNA phosphodiesterase 1 inhibitors and their anticancer activity.Bioorganic chemistry · 2022Article
- SLFN11 is Widely Expressed in Pediatric Sarcoma and Induces Variable Sensitization to Replicative Stress Caused By DNA-Damaging Agents.Molecular cancer therapeutics · 2021Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Clinical topoisomerase I (Top1) and II (Top2) inhibitors trap topoisomerases on DNA, thereby inducing protein-linked DNA breaks. Cancer cells resist the drugs by removing topoisomerase-DNA complexes, and repairing the drug-induced DNA double-strand breaks (DSB) by homologous recombination and nonhomologous end joining (NHEJ). Because numerous enzymes and cofactors are involved in the removal of the topoisomerase-DNA complexes and DSB repair, it has been challenging to comprehensively analyze the relative contribution of multiple genetic pathways in vertebrate cells. Comprehending the relative contribution of individual repair factors would give insights into the lesions induced by the inhibitors and genetic determinants of response. Ultimately, this information would be useful to target specific pathways to augment the therapeutic activity of topoisomerase inhibitors. To this end, we put together 48 isogenic DT40 mutant cells deficient in DNA repair and generated one cell line deficient in autophagy (ATG5). Sensitivity profiles were established for three clinically relevant Top1 inhibitors (camptothecin and the indenoisoquinolines LMP400 and LMP776) and three Top2 inhibitors (etoposide, doxorubicin, and ICRF-193). Highly significant correlations were found among Top1 inhibitors as well as Top2 inhibitors, whereas the profiles of Top1 inhibitors were different from those of Top2 inhibitors. Most distinct repair pathways between Top1 and Top2 inhibitors include NHEJ, TDP1, TDP2, PARP1, and Fanconi Anemia genes, whereas homologous recombination seems relevant especially for Top1 and, to a lesser extent, for Top2 inhibitors. We also found and discuss differential pathways among Top1 inhibitors and Top2 inhibitors.
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