ArticleMolecular cancer therapeutics2015
Functional Genetic Screen Identifies Increased Sensitivity to WEE1 Inhibition in Cells with Defects in Fanconi Anemia and HR Pathways.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- miR-15b modulates multidrug resistance in human osteosarcoma in vitro and in vivo.Molecular oncology · 2017Trial
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- Targeting FANCM by antisense oligonucleotides in ALT-positive cancers.Molecular therapy. Nucleic acids · 2025Article
- Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.NPJ precision oncology · 2025Article
- Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.Molecular oncology · 2024Article
- FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe.DNA repair · 2024Article
- A landscape of response to drug combinations in non-small cell lung cancer.Nature communications · 2023Article
- Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023Review
- Review
- Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1.Frontiers in oncology · 2022Review
- Association of Homologous Recombination-DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers.Molecular cancer therapeutics · 2022Article
- Review
- Targeting the replication stress response through synthetic lethal strategies in cancer medicine.Trends in cancer · 2021Review
- Targeting Non-Oncogene Addiction for Cancer Therapy.Biomolecules · 2021Review
- FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Actionable co-alterations in breast tumors with pathogenic mutations in the homologous recombination DNA damage repair pathway.Breast cancer research and treatment · 2020Article
- Review
- PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer.eLife · 2020Article
- Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer.Scientific reports · 2020Article
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 1 institution in 2 countries.
Funding
Abstract
WEE1 kinase regulates CDK1 and CDK2 activity to facilitate DNA replication during S-phase and to prevent unscheduled entry into mitosis. WEE1 inhibitors synergize with DNA-damaging agents that arrest cells in S-phase by triggering direct mitotic entry without completing DNA synthesis, resulting in catastrophic chromosome fragmentation and apoptosis. Here, we investigated how WEE1 inhibition could be best exploited for cancer therapy by performing a functional genetic screen to identify novel determinants of sensitivity to WEE1 inhibition. Inhibition of kinases that regulate CDK activity, CHK1 and MYT1, synergized with WEE1 inhibition through both increased replication stress and forced mitotic entry of S-phase cells. Loss of multiple components of the Fanconi anemia (FA) and homologous recombination (HR) pathways, in particular DNA helicases, sensitized to WEE1 inhibition. Silencing of FA/HR genes resulted in excessive replication stress and nucleotide depletion following WEE1 inhibition, which ultimately led to increased unscheduled mitotic entry. Our results suggest that cancers with defects in FA and HR pathways may be targeted by WEE1 inhibition, providing a basis for a novel synthetic lethal strategy for cancers harboring FA/HR defects.
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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.