ArticleCancer biology & therapy2014
Abrogating G₂/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Effects of Autophagy Inhibition by SAR405, a Selective VPS34 Inhibitor, on Pleural Mesothelioma Cells.Thoracic cancer · 2026Article
- Targeting Wee1 kinase to suppress proliferation and survival of cisplatin-resistant head and neck squamous cell carcinoma.Cancer chemotherapy and pharmacology · 2022Article
- Combined Analysis of RNA Sequence and Microarray Data Reveals a Competing Endogenous RNA Network as Novel Prognostic Markers in Malignant Pleural Mesothelioma.Frontiers in oncology · 2021Article
- Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of theInternational journal of molecular sciences · 2020Article
- Article
- Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma.Therapeutic advances in medical oncology · 2020Review
- Therapeutic Landscape of Malignant Pleural Mesothelioma: Collateral Vulnerabilities and Evolutionary Dependencies in the Spotlight.Frontiers in oncology · 2020Review
- Cyclin E Overexpression Sensitizes Triple-Negative Breast Cancer to Wee1 Kinase Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Non-ablative hypofractionated hemithoracic radiation-a new standard of care in mesothelioma?Journal of thoracic disease · 2018Article
- Targeting AXL and mTOR Pathway Overcomes Primary and Acquired Resistance to WEE1 Inhibition in Small-Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- A Small-Molecule Inhibitor of WEE1, AZD1775, Synergizes with Olaparib by Impairing Homologous Recombination and Enhancing DNA Damage and Apoptosis in Acute Leukemia.Molecular cancer therapeutics · 2017Article
- Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.Oncotarget · 2017Article
- Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors.Oncotarget · 2015Article
- Sensitization of Pancreatic Cancers to Gemcitabine Chemoradiation by WEE1 Kinase Inhibition Depends on Homologous Recombination Repair.Neoplasia (New York, N.Y.) · 2015Article
- WEE1 kinase polymorphism as a predictive biomarker for efficacy of platinum-gemcitabine doublet chemotherapy in advanced non-small cell lung cancer patients.Scientific reports · 2015Article
- WEE1 murine deficiency induces hyper-activation of APC/C and results in genomic instability and carcinogenesis.Oncogene · 2015Article
- Not so WEE: targeting G₂/M to kill mesothelioma cells.Cancer biology & therapy · 2014Article
- Wee1 kinase inhibitor adavosertib with radiation in newly diagnosed diffuse intrinsic pontine glioma: A Children's Oncology Group phase I consortium study.Neuro-oncology advancesArticle
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant mesothelioma (MM) is a very aggressive asbestos-related neoplasm of the serous membranes, whose incidence is increasing worldwide. Although the introduction of new drug combinations, such as cisplatin plus pemetrexed/gemcitabine, has determined an improvement in the patient quality of life, MM remains a universally fatal disease. The observation that key G 1/S checkpoint regulators are often functionally inactivated in MM prompted us to test whether the use of G 2/M checkpoint inhibitors, able to sensitize G 1/S checkpoint-defective cancer cells to DNA-damaging agents, could be successful in MM. We treated six MM cell lines, representative of different histotypes (epithelioid, biphasic, and sarcomatoid), with cisplatin in combination with MK-1775, an inhibitor of the G 2/M checkpoint kinase WEE1. We observed that MK-1775 enhanced the cisplatin cytotoxic effect in all MM cell lines, except the sarcomatoid cell line, which is representative of the most aggressive histotype. As expected, the enhancement in cisplatin toxicity was accompanied by a decrease in the inactive phosphorylated form of cyclin-dependent kinase 1 (CDK1), a key substrate of WEE1, which is indicative of G 2/M checkpoint inactivation. Consistently, we also observed a decrease in G 2/M accumulation and an increase in mitotic entry of DNA-damaged cells and apoptosis, probably due to the loss of the cell ability to arrest cell cycle in response to DNA damage, irrespectively of p53 mutational status. Notably, this treatment did not increase cisplatin cytotoxicity on normal cells, thus suggesting a possible use of MK-1775 in combination with cisplatin for a safe and efficient treatment of epithelioid and biphasic MM.
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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.