ArticleCell death & disease2023
Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Molecular targeted therapy in combination with chemotherapy for the treatment of platinum-resistant/refractory ovarian cancer (PROC): a systematic review and network meta-analysis.Annals of medicine · 2026Pooled it
- Protein kinase WEE1 promotes cardiomyocytes ferroptosis and cardiac hypertrophy via the NF-κB/LCN2 axis.Acta pharmacologica Sinica · 2026Article
- The lysine methyltransferase KMT5a and p53 regulate the expression of the key autophagy adaptor p62/SQSTM1 in glioblastoma.Cell communication and signaling : CCS · 2026Article
- Article
- Impact of SETD8/KMT5A overexpression on hepatocellular carcinoma progression and prognosis.PloS one · 2026Article
- SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Multiple functions of the lysine methyltransferase KMT5a in cancer: potential targets for innovative therapies.Clinical epigenetics · 2025Review
- Genome editing or small molecule inhibition of KMT5A in CAR-T cells enhances antitumor immunity.Journal for immunotherapy of cancer · 2025Article
- DNA methylation remodeling in temozolomide resistant recurrent glioblastoma: comparing epigenetic dynamics in vitro and in vivo.Journal of translational medicine · 2025Article
- SETD8 inhibits apoptosis and ferroptosis of Ewing's sarcoma through YBX1/RAC3 axis.Cell death & disease · 2024Article
- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite intense research efforts, glioblastoma remains an incurable brain tumor with a dismal median survival time of 15 months. Thus, identifying new therapeutic targets is an urgent need. Here, we show that the lysine methyltransferase SETD8 is overexpressed in 50% of high-grade gliomas. The small molecule SETD8 inhibitor UNC0379, as well as siRNA-mediated inhibition of SETD8, blocked glioblastoma cell proliferation, by inducing DNA damage and activating cell cycle checkpoints. Specifically, in p53-proficient glioblastoma cells, SETD8 inhibition and DNA damage induced p21 accumulation and G1/S arrest whereas, in p53-deficient glioblastoma cells, DNA damage induced by SETD8 inhibition resulted in G2/M arrest mediated by Chk1 activation. Checkpoint abrogation, by the Wee1 kinase inhibitor adavosertib, induced glioblastoma cell lines and primary cells, DNA-damaged by UNC0379, to progress to mitosis where they died by mitotic catastrophe. Finally, UNC0379 and adavosertib synergized in restraining glioblastoma growth in a murine xenograft model, providing a strong rationale to further explore this novel pharmacological approach for adjuvant glioblastoma treatment.
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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 Socratic graph.