Trial reportProceedings of the National Academy of Sciences of the United States of America2013
PML mediates glioblastoma resistance to mammalian target of rapamycin (mTOR)-targeted therapies.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 64 citations in OpenAlex.
- A phase II trial of arsenic trioxide and temozolomide in combination with radiation therapy for patients with malignant gliomas.Journal of neuro-oncology · 2017Trial
- Precision post-translational modification of PML defines neuroblastoma clinical behaviour.Clinical and translational medicine · 2026Article
- Cryo-EM structure of PML RBCC dimer reveals CC-mediated octopus-like nuclear body assembly mechanism.Cell discovery · 2024Article
- PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma.EMBO molecular medicine · 2024Article
- The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.Cell death and differentiation · 2024Article
- PML Body Biogenesis: A Delicate Balance of Interactions.International journal of molecular sciences · 2023Review
- Review
- Deciphering specific miRNAs in brain tumors: a 5-miRNA signature in glioblastoma.Molecular genetics and genomics : MGG · 2022Article
- TP53 inhibitor PFTα increases the sensitivity of arsenic trioxide in TP53 wildtype tumor cells.FEBS open bio · 2022Article
- Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial.Medical oncology (Northwood, London, England) · 2021Article
- SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia.The Journal of clinical investigation · 2021Article
- PML Differentially Regulates Growth and Invasion in Brain Cancer.International journal of molecular sciences · 2021Article
- Autophagy mediated lipid catabolism facilitates glioma progression to overcome bioenergetic crisis.British journal of cancer · 2021Article
- Review
- Oncogenic Smurf1 promotes PTEN wild-type glioblastoma growth by mediating PTEN ubiquitylation.Oncogene · 2020Article
- Repurposing Potential of Riluzole as an ITAF Inhibitor in mTOR Therapy Resistant Glioblastoma.International journal of molecular sciences · 2020Article
- The Role of Metabolic Plasticity in Blood and Brain Stem Cell Pathophysiology.Cancer research · 2020Review
- The protein arginine methyltransferase PRMT5 confers therapeutic resistance to mTOR inhibition in glioblastoma.Journal of neuro-oncology · 2019Article
- Article
- PR-LncRNA signature regulates glioma cell activity through expression of SOX factors.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
Abstract
Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstream mTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it.
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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.