ArticleCancer research2020
Combined Inhibition of SHP2 and MEK Is Effective in Models of NF1-Deficient Malignant Peripheral Nerve Sheath Tumors.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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.
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Who cites it
60 citing papers in PubMed, 63 citations in OpenAlex.
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- GATA3-driven CDC20 activation facilitates tumor growth and metastasis through suppressing Bax/Bcl-2 ratio and boosting EMT process in neuroblastoma.The Journal of biological chemistry · 2026Article
- Review
- New Treatment Strategy and Future Research Direction for BRAF-Mutated Cancer.Cancer science · 2026Review
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- MEK inhibitors for neurofibromatosis type 1-associated central and peripheral nervous system tumors.Neuro-oncology advances · 2026Review
- The Cell Surface Proteome of Malignant Peripheral Nerve Sheath Tumors Reveals Therapeutic Targets.bioRxiv : the preprint server for biology · 2026Article
- IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- Pharmacogenomic Synthetic Lethal Screens Reveal Hidden Vulnerabilities and New Therapeutic Approaches for Treatment of NF1-Associated Tumors.Molecular cancer therapeutics · 2026Article
- Review
- TEAD inhibitors synergize with MEK, SHP2 and mTOR inhibitors in NF1 and NF2 cell lines.microPublication biology · 2026Article
- Computational insights into synergistic mechanisms of PD-901 and 5-azacitidine targeting PTPN11 (SHP2) E76K mutation in juvenile myelomonocytic leukemia.Frontiers in bioinformatics · 2026Article
- Midkine as a therapeutic node in NF1-driven neuro‑oncology: Biology, biomarkers, and translational strategies.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Daytime SHP2 inhibitor dosing, when immune cell numbers are elevated, shrinks neurofibromas.Life science alliance · 2025Article
- Review
- Development of an adeno-associated virus vector for gene replacement therapy of NF1-related tumors.Nature communications · 2025Article
- Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors.Molecular medicine (Cambridge, Mass.) · 2025Article
- Tumor heterogeneity underlies clinical outcome and MEK inhibitor response in somatic NF1-mutant glioblastoma.JCI insight · 2025Article
- Infection and herbicide exposure implicate c-Abl kinase in α-Synuclein Ser129 phosphorylation.Cell communication and signaling : CCS · 2025Article
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss of the RAS GTPase-activating protein (RAS-GAP) NF1 drives aberrant activation of RAS/MEK/ERK signaling and other effector pathways in the majority of malignant peripheral nerve sheath tumors (MPNST). These dysregulated pathways represent potential targets for therapeutic intervention. However, studies of novel single agents including MEK inhibitors (MEKi) have demonstrated limited efficacy both preclinically and clinically, with little advancement in overall patient survival. By interrogation of kinome activity through an unbiased screen and targeted evaluation of the signaling response to MEK inhibition, we have identified global activation of upstream receptor tyrosine kinases (RTK) that converges on activation of RAS as a mechanism to limit sensitivity to MEK inhibition. As no direct inhibitors of pan-RAS were available, an inhibitor of the protein tyrosine phosphatase SHP2, a critical mediator of RAS signal transduction downstream of multiple RTK, represented an alternate strategy. The combination of MEKi plus SHP099 was superior to MEKi alone in models of NF1-MPNST, including those with acquired resistance to MEKi. Our findings have immediate translational implications and may inform future clinical trials for patients with MPNST harboring alterations in
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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.