ArticleMolecular cancer therapeutics2013
NF1 deletion generates multiple subtypes of soft-tissue sarcoma that respond to MEK inhibition.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 83 citations in OpenAlex.
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- Pediatric sarcomas: challenges and opportunities.Genes & development · 2026Review
- Pleomorphic Carcinoma With EGFR and Concomitant Mutations Transformed From Lung Adenocarcinoma: A Case Report.Cancer reports (Hoboken, N.J.) · 2026Article
- Case Report: Primary sciatic leiomyosarcoma in a patient with neurofibromatosis type 1.Frontiers in oncology · 2026Article
- Genetic Heterogeneity of Undifferentiated Pleomorphic Sarcoma: Is There Potential for Targeted Therapy?Cancers · 2025Review
- Genetically Modified Mouse Models for Sarcoma Research: A Comprehensive Review.Current oncology reports · 2025Review
- Prioritization of novel agents for further investigation in pediatric non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group.European journal of cancer (Oxford, England : 1990) · 2025Review
- Undifferentiated Pleomorphic Sarcoma in Children and Young Adults: A Comprehensive Clinicopathologic, Genomic, and Epigenetic Comparison With Adult Counterparts.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Novel Therapeutics and the Path Toward Effective Immunotherapy in Malignant Peripheral Nerve Sheath Tumors.Cancers · 2025Review
- MAPK-targeted therapies in non-gastrointestinal stromal tumor soft tissue sarcomas: current landscape and future directions.Frontiers in oncology · 2025Review
- MEK Inhibitors Lead to PDGFR Pathway Upregulation and Sensitize Tumors to RAF Dimer Inhibitors in NF1-Deficient Malignant Peripheral Nerve Sheath Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Malignant Peripheral Nerve Sheath Tumor, a Heterogeneous, Aggressive Cancer with Diverse Biomarkers and No Targeted Standard of Care: Review of the Literature and Ongoing Investigational Agents.Targeted oncology · 2024Review
- CDK4/6 inhibition enhances SHP2 inhibitor efficacy and is dependent upon RB function in malignant peripheral nerve sheath tumors.Science advances · 2023Article
- Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology.Neuro-oncology · 2023Article
- Discrepancies in indel software resolution with somatic CRISPR/Cas9 tumorigenesis models.Scientific reports · 2023Article
- CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- DICER1-associated central nervous system sarcoma: A comprehensive clinical and genomic characterization of case series of young adult patients.Neuro-oncology practice · 2023Article
- CDK4/6 inhibition enhances SHP2 inhibitor efficacy and is dependent upon restoration of RB function in malignant peripheral nerve sheath tumors.bioRxiv : the preprint server for biology · 2023Article
- Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma.Current issues in molecular biology · 2023Article
- Olfactory groove monophasic sinovial sarcoma and von Recklinghausen's disease: A case report and literature review.Surgical neurology international · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Soft-tissue sarcomas are a heterogeneous group of tumors arising from connective tissue. Recently, mutations in the neurofibromin 1 (NF1) tumor suppressor gene were identified in multiple subtypes of human soft-tissue sarcomas. To study the effect of NF1 inactivation in the initiation and progression of distinct sarcoma subtypes, we have developed a novel mouse model of temporally and spatially restricted NF1-deleted sarcoma. To generate primary sarcomas, we inject adenovirus containing Cre recombinase into NF1(flox/flox); Ink4a/Arf(flox/flox) mice at two distinct orthotopic sites: intramuscularly or in the sciatic nerve. The mice develop either high-grade myogenic sarcomas or malignant peripheral nerve sheath tumor (MPNST)-like tumors, respectively. These tumors reflect the histologic properties and spectrum of sarcomas found in patients. To explore the use of this model for preclinical studies, we conducted a study of mitogen-activated protein kinase (MAPK) pathway inhibition with the MEK inhibitor PD325901. Treatment with PD325901 delays tumor growth through decreased cyclin D1 mRNA and cell proliferation. We also examined the effects of MEK inhibition on the native tumor stroma and find that PD325901 decreases VEGFα expression in tumor cells with a corresponding decrease in microvessel density. Taken together, our results use a primary tumor model to show that sarcomas can be generated by loss of NF1 and Ink4a/Arf, and that these tumors are sensitive to MEK inhibition by direct effects on tumor cells and the surrounding microenvironment. These studies suggest that MEK inhibitors should be further explored as potential sarcoma therapies in patients with tumors containing NF1 deletion.
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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.