Trial reportThe American journal of pathology2010
Targeting DNA replication before it starts: Cdc7 as a therapeutic target in p53-mutant breast cancers.
Trial report in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study.European journal of epidemiology · 2022Pooled it
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- EBNA1 inhibitors reveal CDC7 and POU2F1 as direct functional targets in EBV epithelial cancers.mBio · 2026Article
- CDC7 is a targetable regulator of advanced prostate cancer.Scientific reports · 2025Article
- Static magnetic field and alternating magnetic field cytotoxic effects on triple negative breast cancer cell line (MDA-MB-231).Medical oncology (Northwood, London, England) · 2025Article
- GAIN-BRCA: a graph-based AI-net framework for breast cancer subtype classification using multiomics data.Bioinformatics advances · 2025Article
- CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation.Signal transduction and targeted therapy · 2024Article
- Firing of Replication Origins Is Disturbed by a CDK4/6 Inhibitor in a pRb-Independent Manner.International journal of molecular sciences · 2023Article
- Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening.Cell death discovery · 2023Article
- Co-targeting of specific epigenetic regulators in combination with CDC7 potently inhibit melanoma growth.iScience · 2022Article
- Article
- A novel evaluation method for Ki-67 immunostaining in paraffin-embedded tissues.Virchows Archiv : an international journal of pathology · 2021Article
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
- MiR-200a with CDC7 as a direct target declines cell viability and promotes cell apoptosis in Wilm's tumor via Wnt/β-catenin signaling pathway.Molecular and cellular biochemistry · 2021Article
- Identification of key genes unique to the luminal a and basal-like breast cancer subtypes via bioinformatic analysis.World journal of surgical oncology · 2020Article
- Dbf4-Dependent Kinase (DDK)-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A inG3 (Bethesda, Md.) · 2020Article
- Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer.Cancer research · 2020Article
- Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1.Journal of molecular medicine (Berlin, Germany) · 2018Article
- The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy.Frontiers in molecular biosciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Treatment options for triple-receptor negative (ER-/PR-/Her2-) and Her2-overexpressing (ER-/PR-/Her2+) breast cancers with acquired or de novo resistance are limited, and metastatic disease remains incurable. Targeting of growth signaling networks is often constrained by pathway redundancy or growth-independent cancer cell cycles. The cell-cycle protein Cdc7 regulates S phase by promoting DNA replication. This essential kinase acts as a convergence point for upstream growth signaling pathways and is therefore an attractive therapeutic target. We show that increased Cdc7 expression during mammary tumorigenesis is linked to Her2-overexpressing and triple-negative subtypes, accelerated cell cycle progression (P < 0.001), arrested tumor differentiation (P < 0.001), genomic instability (P = 0.019), increasing NPI score (P < 0.001), and reduced disease-free survival (HR = 1.98 [95% CI: 1.27-3.10]; P = 0.003), thus implicating its deregulation in the development of aggressive disease. Targeting Cdc7 with RNAi, we demonstrate that p53-mutant Her2-overexpressing and triple-negative breast cancer cell lines undergo an abortive S phase and apoptotic cell death due to loss of a p53-dependent Cdc7-inhibition checkpoint. In contrast, untransformed breast epithelial cells arrest in G1, remain viable, and are able to resume cell proliferation on recovery of Cdc7 kinase activity. Thus, Cdc7 appears to represent a potent and highly specific anticancer target in Her2-overexpressing and triple-negative breast cancers. Emerging Cdc7 kinase inhibitors may therefore significantly broaden the therapeutic armamentarium for treatment of the aggressive p53-mutant breast cancer subtypes identified in this study.
Indexed as
Identifiers
What OpenQuestion holds
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.