ArticleOncotarget2016
Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
33 citing papers in PubMed, 56 citations in OpenAlex.
- From benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST): a gaming among multiple factors.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
- Efficacy of Trametinib in Neurofibromatosis Type 1-Associated Gastrointestinal Stromal Tumors: A Case Report.JCO precision oncology · 2024Article
- Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.Journal of cell science · 2024Article
- A MEK inhibitor arrests the cell cycle of human conjunctival fibroblasts and improves the outcome of glaucoma filtration surgery.Scientific reports · 2024Article
- Article
- Review
- Synthetic mRNAs; Their Analogue Caps and Contribution to Disease.Diseases (Basel, Switzerland) · 2021Review
- Toward Understanding the Mechanisms of Malignant Peripheral Nerve Sheath Tumor Development.International journal of molecular sciences · 2021Review
- Activation of Receptor Tyrosine Kinases Mediates Acquired Resistance to MEK Inhibition in Malignant Peripheral Nerve Sheath Tumors.Cancer research · 2021Article
- NF1-RAC1 axis regulates migration of the melanocytic lineage.Translational oncology · 2020Article
- KIF11 and KIF15 mitotic kinesins are potential therapeutic vulnerabilities for malignant peripheral nerve sheath tumors.Neuro-oncology advances · 2020Article
- Review
- Combined Targeting of AKT and mTOR Inhibits Proliferation of Human NF1-Associated Malignant Peripheral Nerve Sheath Tumour Cells In Vitro but not in a Xenograft Mouse Model In Vivo.International journal of molecular sciences · 2020Article
- Advancement in research and therapy ofCancer cell international · 2020Review
- Article
- Liver X Receptors and Their Implications in the Physiology and Pathology of the Peripheral Nervous System.International journal of molecular sciences · 2019Review
- The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma.Cancers · 2019Review
- NF1 mutations identify molecular and clinical subtypes of lung adenocarcinomas.Cancer medicine · 2019Article
- Pulmonary hypertension associated with neurofibromatosis type 1.European respiratory review : an official journal of the European Respiratory Society · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 30-50% of individuals with Neurofibromatosis type 1 develop benign peripheral nerve sheath tumors, called plexiform neurofibromas (PNFs). PNFs can undergo malignant transformation to highly metastatic malignant peripheral nerve sheath tumors (MPNSTs) in 5-10% of NF1 patients, with poor prognosis. No effective systemic therapy is currently available for unresectable tumors. In tumors, the NF1 gene deficiency leads to Ras hyperactivation causing the subsequent activation of the AKT/mTOR and Raf/MEK/ERK pathways and inducing multiple cellular responses including cell proliferation. In this study, three NF1-null MPNST-derived cell lines (90-8, 88-14 and 96-2), STS26T sporadic MPNST cell line and PNF-derived primary Schwann cells were used to test responses to AZD8055, an ATP-competitive "active-site" mTOR inhibitor. In contrast to rapamycin treatment which only partially affected mTORC1 signaling, AZD8055 induced a strong inhibition of mTORC1 and mTORC2 signaling in MPNST-derived cell lines and PNF-derived Schwann cells. AZD8055 induced full blockade of mTORC1 leading to an efficient decrease of global protein synthesis. A higher cytotoxic effect was observed with AZD8055 compared to rapamycin in the NF1-null MPNST-derived cell lines with IC50 ranging from 70 to 140 nM and antiproliferative effect was confirmed in PNF-derived Schwann cells. Cell migration was impaired by AZD8055 treatment and cell cycle analysis showed a G0/G1 arrest. Combined effects of AZD8055 and PD0325901 MEK inhibitor as well as BRD4 (BromoDomain-containing protein 4) inhibitors showed a synergistic antiproliferative effect. These data suggest that NF1-associated peripheral nerve sheath tumors are an ideal target for AZD8055 as a single molecule or in combined therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.