ArticleProceedings of the National Academy of Sciences of the United States of America2015
Microtubule-targeting agents augment the toxicity of DNA-damaging agents by disrupting intracellular trafficking of DNA repair proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 180 citations in OpenAlex.
- Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC.Oncotarget · 2016Trial
- Nanoparticle Co-delivery of Microtubule Inhibitors and Cisplatin Overcomes DNA Repair-Mediated Resistance in Head and Neck Cancer.Molecular cancer therapeutics · 2026Article
- DHX9 Inhibition Enhances Paclitaxel Sensitivity by Inducing Mitotic Failure in Ovarian and Endometrial Cancers.Molecular cancer therapeutics · 2026Article
- Stiffness-dependent alveolar type II cell senescence in idiopathic pulmonary fibrosis.Cell communication and signaling : CCS · 2026Article
- Drug resistance to antibody-drug conjugates: mechanisms, challenges, and perspectives.Cancer biology & medicine · 2026Review
- Roles of cytoskeleton in metastasis: from its mechanism to therapeutic strategies.Experimental & molecular medicine · 2026Review
- KIF2A-mediated microtubule-dependent nuclear envelope invagination drives nonhomologous end joining.Nucleic acids research · 2026Article
- Paclitaxel-induced germline DNA-damage signatures independent of mismatch repair inFrontiers in pharmacology · 2026Article
- Scalable imaging-based profiling of CRISPR perturbations with protein barcodes.bioRxiv : the preprint server for biology · 2025Article
- Cholangiocytes' primary cilia regulate DNA damage response and repair.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Vimentin intermediate filaments orchestrate DNA nonhomologous end joining repair and lipolysis after DNA damage.Oncogene · 2025Article
- Drug-induced second tumors: a disproportionality analysis of the FAERS database.Discover oncology · 2025Article
- Low dose Taxol causes mitochondrial dysfunction in actively respiring cancer cells.The Journal of biological chemistry · 2025Article
- Review
- CITK modulates BRCA1 recruitment at DNA double strand breaks sites through HDAC6.Cell death & disease · 2025Article
- Effective eradication of acute myeloid leukemia stem cells with FLT3-directed antibody-drug conjugates.Leukemia · 2025Article
- Macrocarpal I induces immunogenic cell death and synergizes with immune checkpoint inhibition by targeting tubulin and PARP1 in colorectal cancer.Cell death discovery · 2025Article
- Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.ACS omega · 2025Review
- Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.Journal for immunotherapy of cancer · 2025Article
- Prognostic marker Musashi-2 modulates DNA damage response and radioresistance in diffuse large B-cell lymphoma.Frontiers in cell and developmental biology · 2025Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The paradigm that microtubule-targeting agents (MTAs) cause cell death via mitotic arrest applies to rapidly dividing cells but cannot explain MTA activity in slowly growing human cancers. Many preferred cancer regimens combine a MTA with a DNA-damaging agent (DDA). We hypothesized that MTAs synergize with DDAs by interfering with trafficking of DNA repair proteins on interphase microtubules. We investigated nine proteins involved in DNA repair: ATM, ATR, DNA-PK, Rad50, Mre11, p95/NBS1, p53, 53BP1, and p63. The proteins were sequestered in the cytoplasm by vincristine and paclitaxel but not by an aurora kinase inhibitor, colocalized with tubulin by confocal microscopy and coimmunoprecipitated with the microtubule motor dynein. Furthermore, adding MTAs to radiation, doxorubicin, or etoposide led to more sustained γ-H2AX levels. We conclude DNA damage-repair proteins traffic on microtubules and addition of MTAs sequesters them in the cytoplasm, explaining why MTA/DDA combinations are common anticancer regimens.
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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.