ArticleScience advances2021
A CDC7 inhibitor sensitizes DNA-damaging chemotherapies by suppressing homologous recombination repair to delay DNA damage recovery.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives.Communications biology · 2026Review
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- Jab1 regulates HRR mRNA stability to modulate PARP inhibitor sensitivity in triple-negative breast cancer.Molecular cancer · 2025Article
- PARP inhibitors elicit a cellular senescence mediated inflammatory response in homologous recombination proficient cancer cells.Scientific reports · 2025Article
- Gene expression analysis in circulating tumour cells to determine resistance to CDK4/6 inhibitors plus endocrine therapy in HR + /HER2- metastatic breast cancer patients.Journal of translational medicine · 2025Article
- Death domain-associated protein (Daxx) impairs colon cancer chemotherapy by inhibiting the cGAS-STING pathway.Oncology research · 2025Article
- DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.The Journal of cell biology · 2024Article
- CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation.Signal transduction and targeted therapy · 2024Article
- Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination.Nature communications · 2024Article
- Article
- Discovery of a potent and selective cell division cycle 7 inhibitor from 6-(3-fluoropyridin-4-yl)thieno[3,2-Acta pharmaceutica Sinica. B · 2024Article
- CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade.Nature communications · 2023Article
- A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics.Nature communications · 2023Article
- Drug-tolerant persister cells in cancer: the cutting edges and future directions.Nature reviews. Clinical oncology · 2023Review
- Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening.Cell death discovery · 2023Article
- Germline ERCC excision repair 6 like 2 (ERCC6L2) mutations lead to impaired erythropoiesis and reshaping of the bone marrow microenvironment.British journal of haematology · 2022Article
- MCM2 in human cancer: functions, mechanisms, and clinical significance.Molecular medicine (Cambridge, Mass.) · 2022Review
- 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
- WEE1 inhibition augments CDC7 (DDK) inhibitor-induced cell death in Ewing sarcoma by forcing premature mitotic entry and mitotic catastrophe.Cancer research communications · 2022Article
- Precision Medicine forCancers · 2022Review
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
Cell division cycle 7 (CDC7), a serine/threonine kinase, plays important roles in DNA replication. We developed a highly specific CDC7 inhibitor, TAK-931, as a clinical cancer therapeutic agent. This study aimed to identify the potential combination partners of TAK-931 for guiding its clinical development strategies. Unbiased high-throughput chemical screening revealed that the highest synergistic antiproliferative effects observed were the combinations of DNA-damaging agents with TAK-931. Functional phosphoproteomic analysis demonstrated that TAK-931 suppressed homologous recombination repair activity, delayed recovery from double-strand breaks, and led to accumulation of DNA damages in the combination. Whole-genome small interfering RNA library screening identified sensitivity-modulating molecules, which propose the experimentally predicted target cancer types for the combination, including pancreatic, esophageal, ovarian, and breast cancers. The efficacy of combination therapy in these cancer types was preclinically confirmed in the corresponding primary-derived xenograft models. Thus, our findings would be helpful to guide the future clinical strategies for TAK-931.
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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.