ArticleCancers2018
AZD1775 Increases Sensitivity to Olaparib and Gemcitabine in Cancer Cells with p53 Mutations.
Article in Cancers, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Enhanced pharmacological activities of AKR1C3-activated prodrug AST-3424 in cancer cells with defective DNA repair.International journal of cancer · 2025Article
- Harnessing machine learning to find synergistic combinations for FDA-approved cancer drugs.Scientific reports · 2024Article
- Targeting WEE1 Kinase in Gynecological Malignancies.Drug design, development and therapy · 2024Review
- JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells.Journal of Cancer · 2024Article
- Targeting DNA Damage Repair and Immune Checkpoint Proteins for Optimizing the Treatment of Endometrial Cancer.Pharmaceutics · 2023Review
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- Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.EMBO molecular medicine · 2023Article
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- Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023Review
- Combination DNA Damage Response (DDR) Inhibitors to Overcome Drug Resistance in Ovarian Cancer.Cancer treatment and research · 2023Article
- The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment.Journal of hematology & oncology · 2022Review
- Ricolinostat enhances adavosertib‑induced mitotic catastrophe in TP53‑mutated head and neck squamous cell carcinoma cells.International journal of oncology · 2022Article
- Genomic landscape of advanced endometrial cancer analyzed by targeted next-generation sequencing and the cancer genome atlas (TCGA) dataset.Journal of gynecologic oncology · 2022Article
- Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.Biomolecules · 2022Review
- The Emerging Roles and Therapeutic Implications of Epigenetic Modifications in Ovarian Cancer.Frontiers in endocrinology · 2022Review
- Synthetic Lethality in Ovarian Cancer.Molecular cancer therapeutics · 2021Review
- Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Review
- Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Targeting WEE1 Inhibits Growth of Breast Cancer Cells That Are Resistant to Endocrine Therapy and CDK4/6 Inhibitors.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function. The tyrosine kinase WEE1 regulates cdc2 activity at the G2/M checkpoint and prevents entry into mitosis in response to DNA damage or stalled DNA replication. AZD1775 is a WEE1 inhibitor that overrides and opens the G2/M checkpoint by preventing WEE1-mediated phosphorylation of cdc2 at tyrosine 15. In this study, we assessed the effect of AZD1775 on endometrial and ovarian cancer cells in the presence of two DNA damaging agents, the PARP1 inhibitor, olaparib, and the chemotherapeutic agent, gemcitabine. We show that AZD1775 alone is effective as a therapeutic agent against some p53 mutated cell models. Moreover, the combination of AZD1775 with olaparib or gemcitabine is synergistic in cells with mutant p53 and constitutes a new approach that should be considered in the treatment of advanced and recurrent gynecologic cancer.
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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.