ArticleMolecular cancer therapeutics2015
Identification of novel radiosensitizers in a high-throughput, cell-based screen for DSB repair inhibitors.
Article in Molecular cancer therapeutics, 2015. 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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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.Cancer science · 2026Article
- The Combination of PARP and Topoisomerase 1 Inhibitors Improves Radiation Therapy for Ewing Sarcoma.Cancer science · 2025Article
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- ZEB1 promotes non-homologous end joining double-strand break repair.Nucleic acids research · 2023Article
- Development of a G2/M arrest high-throughput screening method identifies potent radiosensitizers.Translational oncology · 2022Article
- High-Content Clonogenic Survival Screen to Identify Chemoradiation Sensitizers.International journal of radiation oncology, biology, physics · 2021Article
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.Signal transduction and targeted therapy · 2021Review
- Article
- Nrf2 inhibition sensitizes breast cancer stem cells to ionizing radiation via suppressing DNA repair.Free radical biology & medicine · 2021Article
- Article
- Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore.Oncotarget · 2021Article
- An Alternative Pipeline for Glioblastoma Therapeutics: A Systematic Review of Drug Repurposing in Glioblastoma.Cancers · 2021Review
- HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation.Molecular cancer therapeutics · 2018Article
- GBM radiosensitizers: dead in the water…or just the beginning?Journal of neuro-oncology · 2017Review
- The evolving role for re-irradiation in the management of recurrent grade 4 glioma.Journal of neuro-oncology · 2017Review
- Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas.Molecular cancer therapeutics · 2017Article
- 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity.Science translational medicine · 2017Article
- Article
- DNA repair targeted therapy: The past or future of cancer treatment?Pharmacology & therapeutics · 2016Review
- Characterization of Cardiac Glycoside Natural Products as Potent Inhibitors of DNA Double-Strand Break Repair by a Whole-Cell Double Immunofluorescence Assay.Journal of the American Chemical Society · 2016Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved to repair these lesions, and successful DSB repair is essential for tumor cell survival after exposure to ionizing radiation (IR) and other DNA-damaging agents. As such, inhibition of DNA repair is a potentially efficacious strategy for chemo- and radiosensitization. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. Here, we report the design and execution of a high-throughput, cell-based small molecule screen for novel DSB repair inhibitors. We miniaturized our recently developed dual NHEJ and HR reporter system into a 384-well plate-based format and interrogated a diverse library of 20,000 compounds for molecules that selectively modulate NHEJ and HR repair in tumor cells. We identified a collection of novel hits that potently inhibit DSB repair, and we have validated their functional activity in a comprehensive panel of orthogonal secondary assays. A selection of these inhibitors was found to radiosensitize cancer cell lines in vitro, which suggests that they may be useful as novel chemo- and radio sensitizers. Surprisingly, we identified several FDA-approved drugs, including the calcium channel blocker mibefradil dihydrochloride, that demonstrated activity as DSB repair inhibitors and radiosensitizers. These findings suggest the possibility for repurposing them as tumor cell radiosensitizers in the future. Accordingly, we recently initiated a phase I clinical trial testing mibefradil as a glioma radiosensitizer.
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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.