ArticleLeukemia research2018
Increased activity of both CDK1 and CDK2 is necessary for the combinatorial activity of WEE1 inhibition and cytarabine.
Article in Leukemia research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Discovery of Anticancer Indole-Based 4,5-Dihydroisoxazole Derivative with Selectivity toward Leukemia Cells.ACS pharmacology & translational science · 2025Article
- Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas.International journal of cancer · 2025Article
- Synergistic antitumor effect of MK-1775 and CUDC-907 against prostate cancer.Investigational new drugs · 2025Article
- Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases.Signal transduction and targeted therapy · 2024Article
- Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia.Cell reports. Medicine · 2024Article
- Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth.Cell death & disease · 2023Article
- Emerging Targets in Clear Cell Renal Cell Carcinoma.Cancers · 2022Review
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Inhibition of the ATR-CHK1 Pathway in Ewing Sarcoma Cells Causes DNA Damage and Apoptosis via the CDK2-Mediated Degradation of RRM2.Molecular cancer research : MCR · 2020Article
- Increased HDAC Activity and c-MYC Expression Mediate Acquired Resistance to WEE1 Inhibition in Acute Leukemia.Frontiers in oncology · 2020Article
- SETD2 mutations confer chemoresistance in acute myeloid leukemia partly through altered cell cycle checkpoints.Leukemia · 2019Article
- Multiple Defects Sensitize p53-Deficient Head and Neck Cancer Cells to the WEE1 Kinase Inhibition.Molecular cancer research : MCR · 2019Article
- Premature activation of Cdk1 leads to mitotic events in S phase and embryonic lethality.Oncogene · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Inhibition of WEE1 is emerging as a promising chemosensitization strategy in many cancers including acute leukemia. Our lab and others have demonstrated that a small-molecule inhibitor of WEE1, AZD1775, sensitizes acute leukemia cells to cytarabine; however, a mechanism of combinatorial activity has remained elusive. Thus, we sought to determine the relative contribution of WEE1 targets CDK1 and CDK2 to the combinatorial activity of AZD1775 and cytarabine. To accomplish this, we expressed "WEE1 resistant" CDK1 (CDK1-AF) and CDK2 (CDK2-AF) constructs in a T-ALL cell line. Expression of CDK1/2-AF together, but neither alone, enhanced the anti-proliferative effects, DNA damage and apoptosis induced by cytarabine. Furthermore, pharmacologic inhibition of CDK1 alone or CDK1 and CDK2 together reduced the combinatorial activity of AZD1775 and cytarabine. Thus, increased activity of both CDK1 and CDK2 in response to WEE1 inhibition is necessary for the combinatorial activity of AZD1775 and cytarabine. This suggests the role of WEE1 in cells with accumulated DNA damage extends beyond regulation of CDK1 and the G2/M checkpoint and highlights the importance of WEE1 in mediating progression through the cell cycle.
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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.