ArticleRadiation oncology (London, England)2023
G2 checkpoint targeting via Wee1 inhibition radiosensitizes EGFRvIII-positive glioblastoma cells.
Article in Radiation oncology (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Transcriptomic Evidence Identifies Two TMBIM Subgroups with Opposing Prognostic Associations in Glioma.Biology · 2026Article
- Dual Targeting of DNA and EGFR by ZYH005 Induces DNA Damage and Mitotic Catastrophe in Glioblastoma.MedComm · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Construction and validation of a prognostic model for glioma: an analysis based on mismatch repair-related genes and their correlation with clinicopathological features.Translational cancer research · 2025Article
- Targeting Chk1 and Wee1 kinases enhances radiosensitivity of 2D and 3D head and neck cancer models to X-rays and low/high-LET protons.Cell death & disease · 2025Article
- WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation.Current cancer drug targets · 2025Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- Review
- Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders.ACS omega · 2023Review
- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe gene of the Epidermal growth factor receptor (EGFR) is one of the most frequently altered genes in glioblastoma (GBM), with deletions of exons 2-7 (EGFRvIII) being amongst the most common genomic mutations. EGFRvIII is heterogeneously expressed in GBM. We already showed that EGFRvIII expression has an impact on chemosensitivity, replication stress, and the DNA damage response. Wee1 kinase is a major regulator of the DNA damage induced G2 checkpoint. It is highly expressed in GBM and its overexpression is associated with poor prognosis. Since Wee1 inhibition can lead to radiosensitization of EGFRvIII-negative (EGFRvIII-) GBM cells, we asked, if Wee1 inhibition is sufficient to radiosensitize also EGFRvIII-positive (EGFRvIII+) GBM cells.
methodsWe used the clinically relevant Wee1 inhibitor adavosertib and two pairs of isogenetic GBM cell lines with and without endogenous EGFRvIII expression exhibiting different TP53 status. Moreover, human GBM samples displaying heterogenous EGFRvIII expression were analyzed. Expression of Wee1 was assessed by Western blot and respectively immunohistochemistry. The impact of Wee1 inhibition in combination with irradiation on cell cycle and cell survival was analyzed by flow cytometry and colony formation assay.
resultsAnalysis of GBM cells and patient samples revealed a higher expression of Wee1 in EGFRvIII+ cells compared to their EGFRvIII- counterparts. Downregulation of EGFRvIII expression by siRNA resulted in a strong decrease in Wee1 expression. Wee1 inhibition efficiently abrogated radiation-induced G2-arrest and caused radiosensitization, without obvious differences between EGFRvIII- and EGFRvIII+ GBM cells.
conclusionWe conclude that the inhibition of Wee1 is an effective targeting approach for the radiosensitization of both EGFRvIII- and EGFRvIII+ GBM cells and may therefore represent a promising new therapeutic option to increase response to radiotherapy.
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