ArticleOncotarget2016
Combinatorial therapeutic targeting of BMP2 and MEK-ERK pathways in NF1-associated malignant peripheral nerve sheath tumors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Induced pluripotent stem cell-derived models of malignant nerve sheath tumor progression mimic glial to neuro-mesenchymal transition and uncover therapeutic opportunities.Nature communications · 2026Article
- MEK-SHP2 inhibition prevents tibial pseudarthrosis caused byScience translational medicine · 2024Article
- Preclinical Assessment of MEK Inhibitors for Malignant Peripheral Nerve Sheath Tumors Reveals Differences in Efficacy and Adaptive Response.Frontiers in oncology · 2022Article
- Hydrostatic mechanical stress regulates growth and maturation of the atrioventricular valve.Development (Cambridge, England) · 2021Article
- WNT5A inhibition alters the malignant peripheral nerve sheath tumor microenvironment and enhances tumor growth.Oncogene · 2021Article
- MEK inhibitors - novel targeted therapies of neurofibromatosis associated benign and malignant lesions.Biomarker research · 2021Review
- Treatment of malignant peripheral nerve sheath tumors in pediatric NF1 disease.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020Review
- Management of cutaneous neurofibroma: current therapy and future directions.Neuro-oncology advances · 2020Review
- Review
- 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
- Neurofibromin level directs RAS pathway signaling and mediates sensitivity to targeted agents in malignant peripheral nerve sheath tumors.Oncotarget · 2018Article
- Development of 3D culture models of plexiform neurofibroma and initial application for phenotypic characterization and drug screening.Experimental neurology · 2018Article
- Cell activity during peripheral nerve defect repair process using a nerve scaffold.Oncotarget · 2017Article
- Ornithine decarboxylase levels in peripheral nerve sheath tumors from NF1 patients.Neuro-oncology advancesArticle
- Combination of EZH2 and MEK inhibitors as an effective therapy for neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical management of malignant peripheral nerve sheath tumors (MPNSTs) is challenging not only due to its aggressive and invasive nature, but also limited therapeutic options. Using gene expression profiling, our lab identified BMP2-SMAD1/5/8 pathway as a potential therapeutic target for treating MPNSTs. In this study, we explored the therapeutic impact of targeting BMP2-SMAD1/5/8 pathway in conjunction with RAS-MEK-ERK signaling, which is constitutively activated in MPNSTs. Our results indicated that single agent treatment with LDN-193189, a BMP2 Type I receptor inhibitor, did not affect the growth and survival of MPNST cells at biochemically relevant inhibitory concentrations. However, addition of a MEK1/2 inhibitor, selumetinib, to LDN-193189-treated cells resulted in significant inhibition of cell growth and induction of cell death. LDN-193189 at biochemically effective concentrations significantly inhibited motility and invasiveness of MPNST cells, and these effects were enhanced by the addition of selumetinib. Overall, our results advocate for a combinatorial therapeutic approach for MPNSTs that not only targets the growth and survival via inhibition of MEK1/2, but also its malignant spread by suppressing the activation of BMP2-SMAD1/5/8 pathway. Importantly, these studies were conducted in low-passage patient-derived MPNST cells, allowing for an investigation of the effects of the proposed drug treatments in a biologically-relevant context.
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