ArticleCancer gene therapy2011
Unrepairable DNA double-strand breaks initiate cytotoxicity with HSV-TK/ganciclovir.
Article in Cancer gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 23 citations in OpenAlex.
- Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study.Blood advances · 2023Trial
- Host DNA repair factors empower a mechanism of antiviral nucleoside analog resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Host DNA repair factors empower a mechanism of antiviral nucleoside analog resistance.bioRxiv : the preprint server for biology · 2026Article
- Article
- Uncovering transcriptomic landscape alterations of CAN-2409 inFrontiers in medicine · 2023Article
- Harnessing Rift Valley fever virus NSs gene for cancer gene therapy.Cancer gene therapy · 2022Article
- Serotype-dependent recombinant adeno-associated vector (AAV) infection of Epstein-Barr virus-positive B-cells, towards recombinant AAV-based therapy of focal EBV + lymphoproliferative disorders.Virology journal · 2021Article
- A human Myogenin promoter modified to be highly active in alveolar rhabdomyosarcoma drives an effective suicide gene therapy.Cancer gene therapy · 2021Article
- RepurposingTheranostics · 2021Article
- Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets.Frontiers in microbiology · 2019Review
- Article
- RNA Structure Design Improves Activity and Specificity of trans-Splicing-Triggered Cell Death in a Suicide Gene Therapy Approach.Molecular therapy. Nucleic acids · 2018Article
- Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice.Translational psychiatry · 2017Article
- Expression of Herpes Simplex Virus Thymidine Kinase/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells.Molecular therapy. Nucleic acids · 2017Article
- Designing and building oncolytic viruses.Future virology · 2017Review
- The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor.PloS one · 2015Article
- Inhibition of homologous recombination with vorinostat synergistically enhances ganciclovir cytotoxicity.DNA repair · 2013Article
- gef gene expression in MCF-7 breast cancer cells is associated with a better prognosis and induction of apoptosis by p53-mediated signaling pathway.International journal of molecular sciences · 2011Article
- Targeted Inhibitory Effect of Nasopharyngeal Carcinoma Cells by HreTechnology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The herpes simplex virus thymidine kinase (HSV-TK) is the most widely used suicide gene in cancer gene therapy due to its superior anticancer activity with ganciclovir (GCV) compared with other HSV-TK substrates, such as 1-β-D-arabinofuranosyl thymine (araT). We have evaluated the role of DNA damage as a mechanism for the superiority of GCV. Using γ-H2AX foci as an indicator of DNA damage, GCV induced ≥ sevenfold more foci than araT at similar cytotoxic concentrations. The number of foci decreased after removal of either drug, followed by an increase in Rad51 foci indicating that homologous recombination repair (HRR) was used to repair this damage. Notably, only GCV produced a late and persistent increase in γ-H2AX foci demonstrating the induction of unrepairable DNA damage. Both drugs induced the ATR damage response pathway, as evidenced by Chk1 activation. However, GCV resulted in greater activation of ATM, which coincided with the late induction of γ-H2AX foci, demonstrating the presence of DNA double-strand breaks (DSBs). The increase in DSBs after Rad51 induction suggested that they occurred as a result of a failed attempt at HRR. These data demonstrate that the late and unrepairable DSBs observed uniquely with GCV account for its superior cytotoxicity and further suggest that inhibition of HRR will enhance cytotoxicity with HSV-TK/GCV.
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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.