ArticleOncotarget2016
MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting Chk1 and Wee1 kinases enhances radiosensitivity of 2D and 3D head and neck cancer models to X-rays and low/high-LET protons.Cell death & disease · 2025Article
- The Potential for Targeting GCancers · 2024Review
- The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.Nature communications · 2024Article
- LowTheranostics · 2024Article
- Race- associated molecular differences in uterine serous carcinoma.Frontiers in oncology · 2024Article
- Review
- DAP3-mediated cell cycle regulation and its association with radioresistance in human lung adenocarcinoma cell lines.Journal of radiation research · 2023Article
- Death-associated protein 3 in cancer-discrepant roles of DAP3 in tumours and molecular mechanisms.Frontiers in oncology · 2023Review
- The evolving role of DNA damage response in overcoming therapeutic resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Syntaxin 18 regulates the DNA damage response and epithelial-to-mesenchymal transition to promote radiation resistance of lung cancer.Cell death & disease · 2022Article
- Chk1 Inhibition Ameliorates Alzheimer's Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Review
- Inhibition of checkpoint kinase 1 potentiates anticancer activity of gemcitabine in bladder cancer cells.Scientific reports · 2021Article
- Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints.International journal of radiation biology · 2021Article
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- Article
- Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells.Breast cancer research : BCR · 2019Article
- Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells.International journal of molecular sciences · 2019Article
- Functional Precision Medicine Identifies Novel Druggable Targets and Therapeutic Options in Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Clinically Applicable Inhibitors Impacting Genome Stability.Molecules (Basel, Switzerland) · 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
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Radiotherapy is commonly used to treat a variety of solid tumors but improvements in the therapeutic ratio are sorely needed. The aim of this study was to assess the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor cells. Cells derived from NSCLC and HNSCC cancers were tested for radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation-induced G2 block was determined using flow cytometry. Effects on repair of radiation-induced DNA double strand breaks (DSBs) were determined on the basis of rad51, γ-H2AX and 53BP1 foci. Clonogenic survival analyses indicated that MK-8776 radiosensitized p53-defective tumor cells but not lines with wild-type p53. Abrogation of the G2 block was evident in both p53-defective cells and p53 wild-type lines indicating no correlation with radiosensitization. However, only p53-defective cells entered mitosis harboring unrepaired DSBs. MK-8776 appeared to inhibit repair of radiation-induced DSBs at early times after irradiation. A comparison of MK-8776 to the wee1 inhibitor, MK-1775, suggested both similarities and differences in their activities. In conclusion, MK-8776 radiosensitizes tumor cells by mechanisms that include abrogation of the G2 block and inhibition of DSB repair. Our findings support the clinical evaluation of MK-8776 in combination with radiation.
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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.