ArticleMolecular cancer therapeutics2008
Sorafenib inhibits growth and mitogen-activated protein kinase signaling in malignant peripheral nerve sheath cells.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Phase II study of sorafenib in patients with metastatic or recurrent sarcomas.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors.Molecular medicine (Cambridge, Mass.) · 2025Article
- MAPK-targeted therapies in non-gastrointestinal stromal tumor soft tissue sarcomas: current landscape and future directions.Frontiers in oncology · 2025Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Malignant Peripheral Nerve Sheath Tumors: Latest Concepts in Disease Pathogenesis and Clinical Management.Cancers · 2023Review
- Review
- ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology.Journal of cellular and molecular medicine · 2021Article
- Toward Understanding the Mechanisms of Malignant Peripheral Nerve Sheath Tumor Development.International journal of molecular sciences · 2021Review
- Synthesis of new thienylpicolinamidine derivatives and possible mechanisms of antiproliferative activity.RSC advances · 2020Article
- Article
- Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile.RSC advances · 2020Article
- The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.Expert review of anticancer therapy · 2019Review
- Malignant Peripheral Nerve Sheath Tumors: From Epigenome to Bedside.Molecular cancer research : MCR · 2019Review
- Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for malignant peripheral nerve sheath tumor.Cancer medicine · 2018Article
- Testing ATRA and MEK inhibitor PD0325901 effectiveness in a nude mouse model for human MPNST xenografts.BMC research notes · 2018Article
- Targeted inhibition of glutaminase as a potential new approach for the treatment ofOncotarget · 2017Article
- Drug sensitivity and resistance testing identifies PLK1 inhibitors and gemcitabine as potent drugs for malignant peripheral nerve sheath tumors.Molecular oncology · 2017Article
- Sorafenib combined with HER-2 targeted vaccination can promote effective T cell immunity in vivo.International immunopharmacology · 2017Article
- Photothermal therapy improves the efficacy of a MEK inhibitor in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Malignant peripheral nerve sheath tumors (MPNST) are soft-tissue tumors with a very poor prognosis and largely resistant to chemotherapy. MPNSTs are characterized by activation of the Ras pathway by loss of tumor suppressor neurofibromatosis type 1. In view of this, MPNST may be susceptible to inhibition of the activated Ras/Raf/mitogen-activated protein kinase pathway by the B-Raf inhibitor sorafenib. MPNST (MPNST and ST8814) and dedifferentiated liposarcoma (LS141 and DDLS) human tumor cell lines were characterized for Ras activation and B-Raf expression. Tumor cells were treated with sorafenib and examined for growth inhibition, inhibition of phospho-MEK, phospho-ERK, cell cycle arrest, and changes in cyclin D1 and pRb expression. MPNSTs were sensitive to sorafenib at nanomolar concentrations. This appeared to be due to inhibition of phospho-MEK, phospho-ERK, suppression of cyclin D1, and hypophosphorylation of pRb at the CDK4-specific sites, resulting in a G(1) cell cycle arrest. These effects were not seen in the liposarcoma cells, which either did not express B-Raf or showed decreased Ras activation. Small interfering RNA-mediated depletion of B-Raf in MPNSTs also induced a G(1) cell cycle arrest in these cells, with a marked inhibition of cyclin D1 expression and Rb phosphorylation, whereas depletion of C-Raf did not affect either. With growth inhibition at the low nanomolar range, sorafenib, by inhibiting the mitogen-activated protein kinase pathway, may prove to be a novel therapy for patients with MPNST.
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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.