ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Targeted therapy for BRAFV600E malignant astrocytoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.
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Who cites it
96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 citations in OpenAlex.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.Cancer cell · 2017Pooled it
- Efficacy Study of Vemurafenib in Children With Recurrent or Progressive BRAFJCO precision oncology · 2026Article
- A Cuproptosis-Related lncRNA Signature Predicts Prognosis and Shapes the Immune Landscape in Primary Lower-Grade Glioma.Genetics research · 2025Article
- Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma.Translational cancer research · 2024Article
- A novel BRAF::PTPRN2 fusion in meningioma: a case report.Acta neuropathologica communications · 2023Article
- Successes and challenges in modeling heterogeneous BRAFFrontiers in oncology · 2023Review
- BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.Frontiers in oncology · 2023Review
- H3.3-G34 mutations impair DNA repair and promote cGAS/STING-mediated immune responses in pediatric high-grade glioma models.The Journal of clinical investigation · 2022Article
- BRAF inhibitors in BRAFV600E-mutated pediatric high-grade gliomas: Upfront or at recurrence?Neuro-oncology · 2022Article
- The Intricate Epigenetic and Transcriptional Alterations in Pediatric High-Grade Gliomas: Targeting the Crosstalk as the Oncogenic Achilles' Heel.Biomedicines · 2022Review
- Resistance mechanisms in BRAFFrontiers in oncology · 2022Review
- Patient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma.Nature communications · 2021Article
- Imaging of brain tumors in children: the basics-a narrative review.Translational pediatrics · 2021Review
- Contemporary Mouse Models in Glioma Research.Cells · 2021Review
- Article
- Additional genetic alterations in BRAF-mutant gliomas correlate with histologic diagnoses.Journal of neuro-oncology · 2020Article
- Article
- Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma.Journal of neurology · 2020Article
- Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains.Oncogene · 2020Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeMalignant astrocytomas (MA) are aggressive central nervous system tumors with poor prognosis. Activating mutation of BRAF (BRAF(V600E)) has been reported in a subset of these tumors, especially in children. We have investigated the incidence of BRAF(V600E) in additional pediatric patient cohorts and examined the effects of BRAF blockade in preclinical models of BRAF(V600E) and wild-type BRAF MA. EXPERIMENTAL
designBRAF(V600E) mutation status was examined in two pediatric MA patient cohorts. For functional studies, BRAF(V600E) MA cell lines were used to investigate the effects of BRAF shRNA knockdown in vitro, and to investigate BRAF pharmacologic inhibition in vitro and in vivo.
resultsBRAF(V600E) mutations were identified in 11 and 10% of MAs from two distinct series of tumors (six of 58 cases total). BRAF was expressed in all MA cell lines examined, among which BRAF(V600E) was identified in four instances. Using the BRAF(V600E)-specific inhibitor PLX4720, pharmacologic blockade of BRAF revealed preferential antiproliferative activity against BRAF(V600E) mutant cells in vitro, in contrast to the use of shRNA-mediated knockdown of BRAF, which inhibited cell growth of glioma cell lines regardless of BRAF mutation status. Using orthotopic MA xenografts, we show that PLX4720 treatment decreases tumor growth and increases overall survival in mice-bearing BRAF(V600E) mutant xenografts, while being ineffective, and possibly tumor promoting, against xenografts with wild-type BRAF.
conclusionsOur results indicate a 10% incidence of activating BRAF(V600E) among pediatric MAs. With regard to implications for therapy, our results support evaluation of BRAF(V600E)-specific inhibitors for treating BRAF(V600E) MA patients.
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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.