ArticleThe Journal of clinical investigation2011
Genomic DNA damage and ATR-Chk1 signaling determine oncolytic adenoviral efficacy in human ovarian cancer cells.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.NAR cancer · 2026Article
- Viral rewiring of DDR signaling activates a pro-survival network that drives chemotherapy resistance.bioRxiv : the preprint server for biology · 2026Article
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation.bioRxiv : the preprint server for biology · 2026Article
- Review
- Uncovering ShuangZi Powder's Anti-Ovarian Cancer Mechanism: A Systems Biology and Experimental Approach.Combinatorial chemistry & high throughput screening · 2026Article
- The adenovirus E4orf1 protein initiates a feedback loop involving insulin and growth factor receptors, AKT, and NF-κB, leading to abnormal DNA content in infected cells.PLoS pathogens · 2025Article
- Tailoring an intravenously injectable oncolytic virus for augmenting radiotherapy.Cell reports. Medicine · 2025Article
- The diel disconnect between cell growth and division inFrontiers in microbiology · 2024Article
- Targeting the Retinoblastoma/E2F repressive complex by CDK4/6 inhibitors amplifies oncolytic potency of an oncolytic adenovirus.Nature communications · 2022Article
- Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-κB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n.Microbiology spectrum · 2022Article
- Carvedilol targets β-arrestins to rewire innate immunity and improve oncolytic adenoviral therapy.Communications biology · 2022Article
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- Review
- RIPK3 promotes adenovirus type 5 activity.Cell death & disease · 2017Article
- The E1B19K-deleted oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11.Oncotarget · 2016Article
- Activation of Cyclic Adenosine Monophosphate Pathway Increases the Sensitivity of Cancer Cells to the Oncolytic Virus M1.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- RAD51 and BRCA2 Enhance Oncolytic Adenovirus Type 5 Activity in Ovarian Cancer.Molecular cancer research : MCR · 2016Article
- Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control.Molecular oncology · 2015Article
- PARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro and in vivo model of anaplastic thyroid carcinoma.Molecular oncology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Oncolytic adenoviruses replicate selectively within and lyse malignant cells. As such, they are being developed as anticancer therapeutics. However, the sensitivity of ovarian cancers to adenovirus cytotoxicity varies greatly, even in cells of similar infectivity. Using both the adenovirus E1A-CR2 deletion mutant dl922-947 and WT adenovirus serotype 5 in a panel of human ovarian cancer cell lines that cover a 3-log range of sensitivity, we observed profound overreplication of genomic DNA only in highly sensitive cell lines. This was associated with the presence of extensive genomic DNA damage. Inhibition of ataxia telangiectasia and Rad3-related checkpoint kinase 1 (ATR-Chk1), but not ataxia telangiectasia mutated (ATM), promoted genomic DNA damage and overreplication in resistant and partially sensitive cells. This was accompanied by increased adenovirus cytotoxicity both in vitro and in vivo in tumor-bearing mice. We also demonstrated that Cdc25A was upregulated in highly sensitive ovarian cancer cell lines after adenovirus infection and was stabilized after loss of Chk1 activity. Knockdown of Cdc25A inhibited virus-induced DNA damage in highly sensitive cells and blocked the effects of Chk1 inhibition in resistant cells. Finally, inhibition of Chk1 decreased homologous recombination repair of virus-induced genomic DNA double-strand breaks. Thus, virus-induced host cell DNA damage signaling and repair are key determinants of oncolytic adenoviral activity, and promoting unscheduled DNA synthesis and/or impeding homologous recombination repair could potentiate the effects of oncolytic adenoviruses in the treatment of ovarian cancer.
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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.