ArticleJournal of neuro-oncology2016
Survival advantage combining a BRAF inhibitor and radiation in BRAF V600E-mutant glioma.
Article in Journal of neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 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
- Practical management of BRAF inhibitors in glioma: toxicity and resistance.CNS oncology · 2026Review
- BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFCell reports. Medicine · 2025Article
- Unveiling radiobiological traits and therapeutic responses of BRAFJournal of experimental & clinical cancer research : CR · 2025Article
- Radiotherapy for pediatric low-grade glioma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors.Journal of neuro-oncology · 2023Article
- Molecular Heterogeneity in BRAF-Mutant Gliomas: Diagnostic, Prognostic, and Therapeutic Implications.Cancers · 2023Review
- Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.Cancers · 2023Review
- Targeting RAS-RAF-MEK-ERK signaling pathway in human cancer: Current status in clinical trials.Genes & diseases · 2023Review
- Successes and challenges in modeling heterogeneous BRAFFrontiers in oncology · 2023Review
- Translation of Precision Medicine Research Into Biomarker-Informed Care in Radiation Oncology.Seminars in radiation oncology · 2022Review
- Phenformin and ataxia-telangiectasia mutated inhibitors synergistically co-suppress liver cancer cell growth by damaging mitochondria.FEBS open bio · 2021Article
- The Evolving Role of Radiotherapy for Pediatric Cancers With Advancements in Molecular Tumor Characterization and Targeted Therapies.Frontiers in oncology · 2021Review
- Radiation in Combination With Targeted Agents and Immunotherapies for Pediatric Central Nervous System Tumors - Progress, Opportunities, and Challenges.Frontiers in oncology · 2021Review
- Leptomeningeal Spread in Glioblastoma: Diagnostic and Therapeutic Challenges.The oncologist · 2020Review
- TERT expression is susceptible to BRAF and ETS-factor inhibition in BRAFActa neuropathologica communications · 2019Article
- Inhibiting BRAF Oncogene-Mediated Radioresistance Effectively Radiosensitizes BRAFClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy.Acta neuropathologica communications · 2019Article
- Phenformin as an Anticancer Agent: Challenges and Prospects.International journal of molecular sciences · 2019Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Radiation (RT) is critical to the treatment of high-grade gliomas (HGGs) but cures remain elusive. The BRAF mutation V600E is critical to the pathogenesis of 10-20% of pediatric gliomas, and a small proportion of adult HGGs. Here we aim to determine whether PLX4720, a specific BRAF V600E inhibitor, enhances the activity of RT in human HGGs in vitro and in vivo. Patient-derived HGG lines harboring wild-type BRAF or BRAF V600E were assessed in vitro to determine IC50 values, cell cycle arrest, apoptosis and senescence and elucidate mechanisms of combinatorial activity. A BRAF V600E HGG intracranial xenograft mouse model was used to evaluate in vivo combinatorial efficacy of PLX4720+RT. Tumors were harvested for immunohistochemistry to quantify cell cycle arrest and apoptosis. RT+PLX4720 exhibited greater anti-tumor effects than either monotherapy in BRAF V600E but not in BRAF WT lines. In vitro studies showed increased Annexin V and decreased S phase cells in BRAF V600E gliomas treated with PLX4720+RT, but no significant changes in β-galactosidase levels. In vivo, concurrent and sequential PLX4720+RT each significantly prolonged survival compared to monotherapies, in the BRAF V600E HGG model. Immunohistochemistry of in vivo tumors demonstrated that PLX4720+RT decreased Ki-67 and phospho-MAPK, and increased γH2AX and p21 compared to control mice. BRAF V600E inhibition enhances radiation-induced cytotoxicity in BRAF V600E-mutated HGGs, in vitro and in vivo, effects likely mediated by apoptosis and cell cycle, but not senescence. These studies provide the pre-clinical rationale for clinical trials of concurrent radiotherapy and BRAF V600E inhibitors.
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.