ArticleOncogene2009
CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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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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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.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.
- Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC).Genetics in medicine : official journal of the American College of Medical Genetics · 2022Guideline
- Safety and efficacy of sorafenib therapy in patients with hepatocellular carcinoma: final outcome from the Chinese patient subset of the GIDEON study.Oncotarget · 2016Trial
- Case report: Successful use of MEK inhibitors as an adjuvant approach in the treatment of pediatric MAP4-RAF1 fusion-positive solid tumor.NPJ precision oncology · 2025Article
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.Drugs in R&D · 2024Review
- The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.Nature reviews. Cancer · 2024Review
- Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy.Current medicinal chemistry · 2024Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Unique Spectrum of Activating BRAF Alterations in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- BRAFScience advances · 2023Article
- NaCancer research communications · 2022Article
- Recognition of BRAF by CDC37 and Re-Evaluation of the Activation Mechanism for the Class 2 BRAF-L597R Mutant.Biomolecules · 2022Article
- Acetylation-dependent regulation of BRAF oncogenic function.Cell reports · 2022Article
- Article
- Mitochondrial Metabolism in Melanoma.Cells · 2021Review
- Assessment of RAS Dependency for BRAF Alterations Using Cancer Genomic Databases.JAMA network open · 2021Article
- miR-552 Regulates Liver Tumor-Initiating Cell Expansion and Sorafenib Resistance.Molecular therapy. Nucleic acids · 2020Article
- Review
- AtypicalCancers · 2019Review
- Using molecular dynamics simulation to explore the binding of the three potent anticancer drugs sorafenib, streptozotocin, and sunitinib to functionalized carbon nanotubes.Journal of molecular modeling · 2019Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Here, we identify a panel of melanoma lines with non-V600E mutations in BRAF. These G469E- and D594G-mutated melanomas were found to exhibit constitutive levels of phospho-extracellular signal-regulated kinase (pERK) and low levels of phospho-mitogen-activated protein kinase/ERK kinase (pMEK) and were resistant to MEK inhibition. Upon treatment with the CRAF inhibitor sorafenib, these lines underwent apoptosis and associated with mitochondrial depolarization and relocalization of apoptosis-inducing factor, whereas the BRAF-V600E-mutated melanomas did not. Studies have shown low-activity mutants of BRAF (G469E/D594G) instead signal through CRAF. Unlike BRAF, CRAF directly regulates apoptosis through mitochondrial localization where it binds to Bcl-2 and phosphorylates BAD. The CRAF inhibitor sorafenib was found to induce a time-dependent reduction in both BAD phosphorylation and Bcl-2 expression in the D594G/G469E lines only. Knockdown of CRAF using a lentiviral shRNA suppressed both Bcl-2 expression and induced apoptosis in the D594G melanoma line but not in a V600E-mutated line. Finally, we showed in a series of xenograft studies that sorafenib was more potent at reducing the growth of tumors with the D594G mutation than those with the V600E mutation. In summary, we have identified a group of melanomas with low-activity BRAF mutations that are reliant upon CRAF-mediated survival activity.
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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.