ArticleGenome medicine2021
Targeting CDC7 potentiates ATR-CHK1 signaling inhibition through induction of DNA replication stress in liver cancer.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 37 citations in OpenAlex.
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- Targeting epigenetic regulators induces transcription-replication conflicts to overcome ATR inhibitor resistance.Nucleic acids research · 2026Article
- Replication origin firing capacity indicates ATR inhibitor sensitivity.Nature communications · 2026Article
- Novel driver gene FIRRM regulates the cell cycle for promoting tumor growth in hepatocellular carcinoma.Journal of gastroenterology · 2026Article
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- NCES: A Cell-Specific Network-Augmented Essentiality Framework for Cancer Therapeutic Target Discovery.Computational and structural biotechnology journal · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- RELA Ablation Contributes to Progression of Hepatocellular Carcinoma with TP53Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hepatitis B virus core/capsid protein induces hepatocellular carcinoma progression via long non-coding RNA KCNQ1OT1/miR-335-5p/CDC7 axis.Translational cancer research · 2025Article
- Inferring kinase-phosphosite regulation from phosphoproteome-enriched cancer multi-omics datasets.Briefings in bioinformatics · 2025Article
- Potential promising of synthetic lethality in cancer research and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Genomic Landscape of Wilson Disease in a Pan India Disease Cohort and Population-Scale Data.Movement disorders clinical practice · 2025Article
- MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model.International journal of molecular sciences · 2025Article
- A migrasome-related lncRNA signature predicts prognosis and immune response in hepatocellular carcinoma: Implications for biomarker discovery and therapeutic targeting.Frontiers in pharmacology · 2025Article
- Druggable cavities and allosteric modulators of the cell division cycle 7 (CDC7) kinase.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.Cancer science · 2024Article
- Mitotic catastrophe heterogeneity: implications for prognosis and immunotherapy in hepatocellular carcinoma.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver cancer is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related death worldwide. Broad-spectrum kinase inhibitors like sorafenib and lenvatinib provide only modest survival benefit to patients with hepatocellular carcinoma (HCC). This study aims to identify novel therapeutic strategies for HCC patients.
methodsIntegrated bioinformatics analyses and a non-biased CRISPR loss of function genetic screen were performed to identify potential therapeutic targets for HCC cells. Whole-transcriptome sequencing (RNA-Seq) and time-lapse live imaging were performed to explore the mechanisms of the synergy between CDC7 inhibition and ATR or CHK1 inhibitors in HCC cells. Multiple in vitro and in vivo assays were used to validate the synergistic effects.
resultsThrough integrated bioinformatics analyses using the Cancer Dependency Map and the TCGA database, we identified ATR-CHK1 signaling as a therapeutic target for liver cancer. Pharmacological inhibition of ATR or CHK1 leads to robust proliferation inhibition in liver cancer cells having a high basal level of replication stress. For liver cancer cells that are resistant to ATR or CHK1 inhibition, treatment with CDC7 inhibitors induces strong DNA replication stress and consequently such drugs show striking synergy with ATR or CHK1 inhibitors. The synergy between ATR-CHK1 inhibition and CDC7 inhibition probably derives from abnormalities in mitosis inducing mitotic catastrophe.
conclusionsOur data highlights the potential of targeting ATR-CHK1 signaling, either alone or in combination with CDC7 inhibition, for the treatment of liver cancer.
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