ArticleOncotarget2016
Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 27 citations in OpenAlex.
- Population Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Kinase Inhibitor, in Patients With Advanced Solid Tumors.Journal of clinical pharmacology · 2022Trial
- EBNA1 inhibitors reveal CDC7 and POU2F1 as direct functional targets in EBV epithelial cancers.mBio · 2026Article
- Cell-cycle phase progression analysis identifies three unique phenotypes in soft tissue sarcoma.BMC cancer · 2024Article
- CDC7 as a novel biomarker and druggable target in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Co-targeting of specific epigenetic regulators in combination with CDC7 potently inhibit melanoma growth.iScience · 2022Article
- Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer.Cancer research · 2022Article
- CDC7 Expression in Selected Odontogenic Tumors.International journal of dentistry · 2022Article
- Structural Basis for the Activation and Target Site Specificity of CDC7 Kinase.Structure (London, England : 1993) · 2020Article
- Targeting Inflammation, PHA-767491 Shows a Broad Spectrum in Protein Aggregation Diseases.Journal of molecular neuroscience : MN · 2020Article
- Myc and the Replicative CMG Helicase: The Creation and Destruction of Cancer: Myc Over-Activation of CMG Helicases Drives Tumorigenesis and Creates a Vulnerability in CMGs for Therapeutic Intervention.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Review
- Testing Differential Gene Networks under Nonparanormal Graphical Models with False Discovery Rate Control.Genes · 2020Article
- Differential Sensitivity to CDK2 Inhibition Discriminates the Molecular Mechanisms of CHK1 Inhibitors as Monotherapy or in Combination with the Topoisomerase I Inhibitor SN38.ACS pharmacology & translational science · 2019Article
- CDC7-dependent transcriptional regulation of RAD54L is essential for tumorigenicity and radio-resistance of glioblastoma.Translational oncology · 2018Article
- The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Role of MCM2-7 protein phosphorylation in human cancer cells.Cell & bioscience · 2018Review
- Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in Tumor Tissues Predicted Worse Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma Patients.BioMed research international · 2018Article
- Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion.World journal of gastroenterology · 2017Article
- Chk1 Inhibition of the Replication Factor Drf1 Guarantees Cell-Cycle Elongation at the Xenopus laevis Mid-blastula Transition.Developmental cell · 2017Article
- Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness.Cancer cell international · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCdc7 is a serine/threonine kinase which is responsible for the 'firing' of replication origins leading to initiation of DNA replication. Inhibition or depletion of Cdc7 in normal cells triggers a DNA origin activation checkpoint causing a reversible G1 arrest. Here we investigate Cdc7 as a novel therapeutic target in pancreatic cancer. EXPERIMENTAL
designCdc7 target validation was performed by immunoexpression profiling in a cohort of 73 patients with pancreatic adenocarcinoma including 24 controls. Secondly Cdc7 kinase was targeted in Capan-1 and PANC-1 pancreatic cancer cell line models using either an siRNA against Cdc7 or alternatively a small molecule inhibitor (SMI) of Cdc7 (PHA-767491).
resultsCdc7 was significantly overexpressed in pancreatic adenocarcinoma compared to benign pancreatic tissue (median LI 34.3% vs. 1.3%; P<0.0001). Cdc7 knockdown using siRNA in Capan-1 and PANC-1 cells resulted in marked apoptotic cell death when compared with control cells. A prominent sub-G1 peak was seen on flow cytometry (sub-G1 51% vs. 3% and 45% vs. 0.7% in Capan-1 and PANC-1 cells, respectively). Annexin V labelling confirmed apoptosis in 64% vs. 11% and 75% vs. 8%, respectively. Western blotting showed cleavage of PARP-1 and caspase-3 and presence of γH2A.X. TUNEL assay showed strong staining in treated cells. These results were mirrored following Cdc7 kinase inhibition with PHA-767491.
conclusionsOur findings show that Cdc7 is a potent anti-cancer target in pancreatic adenocarcinoma and that Cdc7 immunoexpression levels might be used as a companion diagnostic to predict response to therapeutic siRNAs or SMIs directed against this kinase.
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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.