ArticleProceedings of the National Academy of Sciences of the United States of America2012
Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Reconstructing the molecular life history of gliomas.Acta neuropathologica · 2018Pooled it
- Palbociclib in Solid Tumor Patients With Genomic Alterations in the cyclinD-cdk4/6-INK4a-Rb Pathway: Results From National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice Trial Arm I (APEC1621I).JCO precision oncology · 2024Trial
- BRAF Inhibition inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma.Journal of neuro-oncology · 2018Trial
- Sox2 protein stability is enhanced by BRafV600E and Pten deletion in adult neural stem/progenitor cells.NPJ precision oncology · 2026Article
- BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFCell reports. Medicine · 2025Article
- BRAF V600E in a preclinical model of pleomorphic Xanthoastrocytoma: Analysis of the tumor microenvironment and immune cell infiltration dynamicsMolecular therapy. Oncology · 2024Article
- Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Successes and challenges in modeling heterogeneous BRAFFrontiers in oncology · 2023Review
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- The evolution of pleomorphic xanthoastrocytoma: from genesis to molecular alterations and mimics.Laboratory investigation; a journal of technical methods and pathology · 2022Review
- NTRK-fusions in pediatric thyroid tumors: Current state and future perspectives.Cancer genetics · 2022Review
- Hypothalamic RaxNature communications · 2021Article
- A phase I trial of the CDK 4/6 inhibitor palbociclib in pediatric patients with progressive brain tumors: A Pediatric Brain Tumor Consortium study (PBTC-042).Pediatric blood & cancer · 2021Article
- Advanced Pediatric Diffuse Pontine Glioma Murine Models Pave the Way towards Precision Medicine.Cancers · 2021Review
- Identifying modules of cooperating cancer drivers.Molecular systems biology · 2021Article
- Wnt-Dependent Oligodendroglial-Endothelial Interactions Regulate White Matter Vascularization and Attenuate Injury.Neuron · 2020Article
- Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAFeLife · 2019Article
- TERT expression is susceptible to BRAF and ETS-factor inhibition in BRAFActa neuropathologica communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 8 institutions in 1 country.
Funding
Abstract
Although malignant astrocytomas are a leading cause of cancer-related death in children, rational therapeutic strategies are lacking. We previously identified activating mutations of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) (BRAF(T1799A) encoding BRAF(V600E)) in association with homozygous cyclin-dependent kinase inhibitor 2A (CDKN2A, encoding p14ARF and p16Ink4a) deletions in pediatric infiltrative astrocytomas. Here we report that BRAF(V600E) expression in neural progenitors (NPs) is insufficient for tumorigenesis and increases NP cellular differentiation as well as apoptosis. In contrast, astrocytomas are readily generated from NPs with additional Ink4a-Arf deletion. The BRAF(V600E) inhibitor PLX4720 significantly increased survival of mice after intracranial transplant of genetically relevant murine or human astrocytoma cells. Moreover, combination therapy using PLX4720 plus the Cyclin-dependent kinase (CDK) 4/6-specific inhibitor PD0332991 further extended survival relative to either monotherapy. Our findings indicate a rational therapeutic strategy for treating a subset of pediatric astrocytomas with BRAF(V600E) mutation and CDKN2A deficiency.
Indexed as
Identifiers
What OpenQuestion holds
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.