ArticleMolecular cancer therapeutics2012
MK1775, a selective Wee1 inhibitor, shows single-agent antitumor activity against sarcoma cells.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 122 citations in OpenAlex.
- miR-15b modulates multidrug resistance in human osteosarcoma in vitro and in vivo.Molecular oncology · 2017Trial
- Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas.PloS one · 2013Trial
- Combination of WEE1 Inhibitor and Vitamin K2 Enhances Therapeutic Efficacy in Chronic Myeloid Leukemia.Cancer innovation · 2025Article
- Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas.International journal of cancer · 2025Article
- Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells.BMC cancer · 2025Article
- Synergistic effects of MK-1775 and gemcitabine on cytotoxicity in non-small cell lung cancer.Heliyon · 2024Article
- WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases withCancers · 2024Article
- New Horizons of Synthetic Lethality in Cancer: Current Development and Future Perspectives.Journal of medicinal chemistry · 2024Review
- Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1.Nature communications · 2023Article
- Targeting WEE1 kinase as a p53-independent therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia.Cancer cell international · 2023Article
- A new wave of innovations within the DNA damage response.Signal transduction and targeted therapy · 2023Review
- A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors.Targeted oncology · 2023Article
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors.Investigational new drugs · 2023Article
- Combination of PARP and WEE1 inhibitorsOncology reports · 2023Article
- SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition.Nature chemical biology · 2023Article
- Review
- Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023Review
- Increased expression of BRD4 isoforms long (BRD4-L) and short (BRD4-S) promotes chemotherapy resistance in high-grade serous ovarian carcinoma.Genes & cancer · 2023Article
- Wee1 promotes cell proliferation and imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-γH2AX-MDC1.Cell communication and signaling : CCS · 2022Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Wee1 is a critical component of the G(2)-M cell-cycle checkpoint control and mediates cell-cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by a selective small molecule inhibitor MK1775 can abrogate G(2)-M checkpoint, resulting in premature mitotic entry and cell death. MK1775 has recently been tested in preclinical and clinical studies of human carcinoma to enhance the cytotoxic effect of DNA-damaging agents. However, its role in mesenchymal tumors, especially as a single agent, has not been explored. Here, we studied the cytotoxic effect of MK1775 in various sarcoma cell lines and patient-derived tumor explants ex vivo. Our data show that MK1775 treatment at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. In MK1775-treated cells, CDC2 activity was enhanced, as determined by decreased inhibitory phosphorylation of tyrosine-15 residue and increased expression of phosphorylated histone H3, a marker of mitotic entry. The cytotoxic effect of Wee1 inhibition on sarcoma cells seems to be independent of p53 status as all sarcoma cell lines with different p53 mutation were highly sensitive to MK1775 treatment. Finally, in patient-derived sarcoma samples, we showed that MK1775 as a single agent causes significant apoptotic cell death, suggesting that Wee1 inhibition may represent a novel approach in the treatment of sarcomas.
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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.