ArticleClinical cancer research : an official journal of the American Association for Cancer Research2018
Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors HarboringJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Targeting RNase H2: A dual-mechanism strategy to elevate replication stress, DNA damage, and antitumor immunity in TNBC.Cell reports. Medicine · 2026Article
- Cyclin E modulates vulnerability to CDC7 kinase inhibition.Oncogenesis · 2026Article
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- Imidazopyridine DSH65 induces intrinsic apoptosis and cell cycle arrest in burkitt lymphoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen.NPJ breast cancer · 2025Article
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- WEE1 inhibition delays resistance to CDK4/6 inhibitor and antiestrogen treatment in ER+ MCF7 cells.NPJ systems biology and applications · 2025Article
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Cobalt-nickel metal-organic frameworks (CNMs) as drug delivery agents for triple-negative breast cancer.Nanoscale advances · 2025Article
- Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update.International journal of molecular sciences · 2025Review
- CCNE1 stabilizes ANLN by counteracting FZR1-mediated the ubiquitination modification to promotes triple negative breast cancer cell stemness and progression.Cell death discovery · 2025Article
- Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR.Nature communications · 2025Article
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.NPJ precision oncology · 2025Article
- Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.Current cancer drug targets · 2025Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
purposePoor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression of cyclin E and phosphorylated-CDK2 are correlated with poor survival in patients with TNBC, and the absence of CDK2 desensitizes cells to inhibition of Wee1 kinase, a key cell-cycle regulator. We hypothesize that cyclin E expression can predict response to therapies, which include the Wee1 kinase inhibitor, AZD1775. EXPERIMENTAL
designMono- and combination therapies with AZD1775 were evaluated in TNBC cell lines and multiple patient-derived xenograft (PDX) models with different cyclin E expression profiles. The mechanism(s) of cyclin E-mediated replicative stress were investigated following cyclin E induction or CRISPR/Cas9 knockout by a number of assays in multiple cell lines.
resultsCyclin E overexpression (i) is enriched in TNBCs with high recurrence rates, (ii) sensitizes TNBC cell lines and PDX models to AZD1775, (iii) leads to CDK2-dependent activation of DNA replication stress pathways, and (iv) increases Wee1 kinase activity. Moreover, treatment of cells with either CDK2 inhibitors or carboplatin leads to transient transcriptional induction of cyclin E (in cyclin E-low tumors) and result in DNA replicative stress. Such drug-mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy.
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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.