ArticleCell reports2017
Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
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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
52 citing papers in PubMed, 105 citations in OpenAlex.
- PRDM1 restricts bladder cancer progression and enhances chemosensitivity by suppressing OTUD6A-mediated deubiquitination of CDC6.Cell death & disease · 2026Article
- SIRT3-IDH2 axis is a target of dietary fructose: implication of IDH2 as a key player in dietary carcinogen toxicity in mice colon.Experimental & molecular medicine · 2025Article
- CDC6 as a pan-cancer immunological and prognostic biomarker and its role in suppressing melanoma malignancy.BMC cancer · 2025Article
- Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer.Scientific reports · 2025Article
- Exploring Bioinformatics Tools to Analyze the Role of CDC6 in the Progression of Polycystic Ovary Syndrome to Endometrial Cancer by Promoting Immune Infiltration.International journal of molecular sciences · 2024Article
- Homologous Recombination Repair Gene Mutations in Prostate Cancer: Prevalence and Clinical Value.Advances in therapy · 2024Review
- Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.Molecular cancer · 2024Article
- Investigating the Role ofCancers · 2024Article
- Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets.Cancers · 2024Review
- CDC6, a key replication licensing factor, is overexpressed and confers poor prognosis in diffuse large B-cell lymphoma.BMC cancer · 2023Article
- A GATA2-CDC6 axis modulates androgen receptor blockade-induced senescence in prostate cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- A kinome-wide CRISPR screen identifies CK1α as a target to overcome enzalutamide resistance of prostate cancer.Cell reports. Medicine · 2023Article
- ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity.BMC cancer · 2023Article
- Prognostic implication of heterogeneity and trajectory progression induced by enzalutamide in prostate cancer.Frontiers in endocrinology · 2023Article
- The functions and roles of C2H2 zinc finger proteins in hepatocellular carcinoma.Frontiers in physiology · 2023Review
- Glutathione-sensitive nanoparticles enhance the combined therapeutic effect of checkpoint kinase 1 inhibitor and cisplatin in prostate cancer.APL bioengineering · 2022Article
- Inhibition ofInternational journal of molecular sciences · 2022Article
- The spectrum of sex differences in cancer.Trends in cancer · 2022Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy. Combination treatment with the AR signaling inhibitor enzalutamide (ENZ) and the Chk1/2 inhibitor AZD7762 demonstrates synergy with regard to inhibition of AR-CDC6-ATR-Chk1 signaling, ATM phosphorylation induction, and apoptosis in VCaP (mutant p53) and LNCaP-C4-2b (wild-type p53) cells. CDC6 overexpression significantly reduced ENZ- and AZD7762-induced apoptosis. Additive or synergistic therapeutic activities are demonstrated in AR-positive animal xenograft models. These findings have important clinical implications, since they introduce a therapeutic strategy for AR-positive, metastatic, castration-resistant PCa, regardless of p53 status, through targeting AR-CDC6-ATR-Chk1 signaling.
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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.