ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 119 citations in OpenAlex.
- Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study.Neuro-oncology · 2016Trial
- PLX3397 Reshapes Hepatic Lipid Metabolism Independent of Microglial Depletion.Neuroscience bulletin · 2026Article
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
- BUB1 an Overexpressed Kinase in Sarcoma: Finding New Target Therapy for Osteosarcoma, Liposarcoma, Synovial Sarcoma, and Leiomyosarcoma.Biomolecules · 2025Article
- The RXR Agonist MSU-42011 Reduces Tumor Burden in a Murine Preclinical NF1-Deficient Model.Cancers · 2025Article
- Loss of neurofibromin induces inflammatory macrophage phenotypic switch and retinal neovascularization via GLUT1 activation.Cell reports · 2025Article
- Article
- A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.Cancers · 2025Review
- Modulating tumor-associated macrophages through CSF1R inhibition: a potential therapeutic strategy for HNSCC.Journal of translational medicine · 2025Article
- Phase II Study of Pexidartinib Plus Sirolimus in Unresectable Malignant Peripheral Nerve Sheath Tumors Identifies M2 Macrophage Activation.JCO oncology advances · 2025Article
- Unveiling the myxofibrosarcoma tumor microenvironment: implications for immunotherapy.Frontiers in immunology · 2025Review
- Multidimensional Immunotyping of Human NF1-Associated Peripheral Nerve Sheath Tumors Uncovers Tumor-Associated Macrophages as Key Drivers of Immune Evasion in the Tumor Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Advanced paternal age exacerbates neuroinflammation in offspring via m6A modification-mediated intergenerational inheritance.Journal of neuroinflammation · 2024Article
- Tumor‑associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review).International journal of oncology · 2024Review
- Exposure to Gulf war illness-related chemicals exacerbates alcohol-induced liver damage in rodents.Scientific reports · 2024Article
- Microglia Suppresses Breast Cancer Brain Metastasis via a Pro-inflammatory Response.Neuroscience bulletin · 2024Article
- Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.International journal of molecular sciences · 2024Article
- TheCancers · 2024Review
- MRI-based Machine Learning Radiomics Can Predict CSF1R Expression Level and Prognosis in High-grade Gliomas.Journal of imaging informatics in medicine · 2024Article
- Exposure to Gulf war illness-related chemicals exacerbates alcohol- induced liver damage in rodents.Research square · 2024Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMalignant peripheral nerve sheath tumor (MPNST) is a highly aggressive tumor type that is resistant to chemotherapy and there are no effective therapies. MPNSTs have been shown to have gene amplification for receptor tyrosine kinases (RTK), PDGFR and c-Kit. We tested the c-Kit inhibitor, imatinib, and PLX3397, a selective c-Fms and c-Kit inhibitor, to evaluate their efficacy against MPNST cells in vitro and in vivo. EXPERIMENTAL
designWe tested the efficacy of imatinib or PLX3397 either alone or in combination with TORC1 inhibitor rapamycin in a cell proliferation assay in vitro and by immunoblotting to determine target inhibition. Immunoblotting and immunohistochemical analysis was further carried out using xenograft samples in vivo.
resultsOur in vitro studies show that imatinib and PLX3397 similarly inhibit cell growth and this can be enhanced with rapamycin with comparable target specificity. However, in vivo studies clearly demonstrate that compared with imatinib, PLX3397 results in sustained blockade of c-Kit, c-Fms, and PDGFRβ, resulting in significant suppression of tumor growth. Moreover, staining for Iba-1, a marker for macrophages, indicates that PLX3397 results in significant depletion of macrophages in the growing tumors. The combination of PLX3397 and rapamycin results in even greater macrophage depletion with continued growth suppression, even when the drug treatment is discontinued.
conclusionsTaken together, our data strongly suggest that PLX3397 is superior to imatinib in the treatment of MPNSTs, and the combination of PLX3397 with a TORC1 inhibitor could provide a new therapeutic approach for the treatment of this disease.
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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.