ArticleInvestigational new drugs2012
Irinotecan and DNA-PKcs inhibitors synergize in killing of colon cancer cells.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- Chloroquine-induced DNA damage synergizes with DNA repair inhibitors causing cancer cell death.Frontiers in oncology · 2024Article
- Radiosensitizing Effects of Irinotecan versus Oxaliplatin Alone and in Combination with 5-Fluorouracil on Human Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer.BMC cancer · 2022Article
- Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity.International journal of molecular sciences · 2022Article
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- Review
- Increased Non-Homologous End Joining Makes DNA-PK a Promising Target for Therapeutic Intervention in Uveal Melanoma.Cancers · 2019Article
- Camptothecin resistance is determined by the regulation of topoisomerase I degradation mediated by ubiquitin proteasome pathway.Oncotarget · 2017Article
- DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles' Heel of Cancer.Biomolecules · 2015Review
- DNA-Dependent Protein Kinase As Molecular Target for Radiosensitization of Neuroblastoma Cells.PloS one · 2015Article
- Simultaneous inhibition of ATR and PARP sensitizes colon cancer cell lines to irinotecan.Frontiers in pharmacology · 2015Article
- Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer.World journal of gastrointestinal oncology · 2014Review
- DNA-dependent protein kinase regulates DNA end resection in concert with Mre11-Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM).The Journal of biological chemistry · 2013Article
- End-joining, translocations and cancer.Nature reviews. Cancer · 2013Review
- The PARP inhibitor ABT-888 synergizes irinotecan treatment of colon cancer cell lines.Investigational new drugs · 2013Article
- Small Molecules, Inhibitors of DNA-PK, Targeting DNA Repair, and Beyond.Frontiers in pharmacology · 2013Article
- PI3K-independent AKT activation in cancers: a treasure trove for novel therapeutics.Journal of cellular physiology · 2012Review
- Effects of the novel DNA dependent protein kinase inhibitor, IC486241, on the DNA damage response to doxorubicin and cisplatin in breast cancer cells.Investigational new drugs · 2012Article
- Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment.Translational cancer research · 2012Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
This study sought to measure the degree of synergy induced by specific small molecule inhibitors of DNA-PK [NU7026 and IC486241 (ICC)], a major component of the non-homologous end-joining (NHEJ) pathway, with SN38 or oxaliplatin. Synergy between the DNA damaging drugs and the DNA-PK inhibitors was assessed using the sulforhodamine-B assay (SRB). Effects of drug combinations on cell cycle and DNA-PK activity were determined using flow cytometry and western blot analysis. DNA damage was assessed via comet assay and quantification of γH2AX. The role of homologous recombination repair (HRR) was determined by nuclear Rad51 protein levels and a GFP reporter recombination assay. Significant reductions in the IC(50) values of SN38 were observed at 5 and 10 μM of DNA-PK inhibitors. Moreover, at 1-2 μM (attainable concentrations with ICC in mice) these DNA-PKcs inhibitors demonstrated synergistic reductions in the IC(50) of SN38. Flow cytometric data indicated that SN38 and SN38 in combination with DNA-PKcs inhibitors showed dramatic G2/M arrest at 24 h. Furthermore, reduced phosphorylation of DNA-PKcs and increased DNA damage were observed at this time point with SN38 in combination with DNA-PKcs inhibitors as compared to cells treated with SN38 alone. SN38 alone and in the presence of ICC increased nuclear Rad51 protein levels. Furthermore, inhibition of DNA-PKcs increased HRR suggesting that NHEJ is a negative regulator of HRR. These data indicate that small molecule inhibitors of DNA-PKcs dramatically enhance the efficacy of SN38 in colon cancer cell lines.
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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.