ArticleCell reports2018
BRAF Splice Variant Resistance to RAF Inhibitor Requires Enhanced MEK Association.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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
28 citing papers in PubMed.
- Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia.British journal of cancer · 2026Article
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Machine learning-based pan-cancer study of classification and mechanism of BRAF inhibitor resistance.Translational cancer research · 2024Article
- Resistance mechanisms of non-small cell lung cancer and improvement of treatment effects through nanotechnology: a narrative review.Journal of thoracic disease · 2024Review
- Review
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- Review
- Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase.Cell communication and signaling : CCS · 2023Article
- Extracellular Vesicles-Based Cell-Cell Communication in Melanoma: New Perspectives in Diagnostics and Therapy.International journal of molecular sciences · 2023Review
- Targeting RAS-RAF-MEK-ERK signaling pathway in human cancer: Current status in clinical trials.Genes & diseases · 2023Review
- BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies.Current treatment options in oncology · 2022Review
- DUSP4 protects BRAF- and NRAS-mutant melanoma from oncogene overdose through modulation of MITF.Life science alliance · 2022Article
- Potential Biomarkers of Skin Melanoma Resistance to Targeted Therapy-Present State and Perspectives.Cancers · 2022Review
- PPP6C, a serine-threonine phosphatase, regulates melanocyte differentiation and contributes to melanoma tumorigenesis through modulation of MITF activity.Scientific reports · 2022Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- Article
- Proteomics and Phosphoproteomics Profiling of Drug-Addicted BRAFi-Resistant Melanoma Cells.Journal of proteome research · 2021Article
- Role of serine 365 in BRAF V600E sensitivity to RAF inhibition.Pigment cell & melanoma research · 2021Article
- Exploiting Allosteric Properties of RAF and MEK Inhibitors to Target Therapy-Resistant Tumors Driven by Oncogenic BRAF Signaling.Cancer discovery · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Expression of aberrantly spliced BRAF V600E isoforms (BRAF V600E ΔEx) mediates resistance in 13%-30% of melanoma patients progressing on RAF inhibitors. BRAF V600E ΔEx confers resistance, in part, through enhanced dimerization. Here, we uncoupled BRAF V600E ΔEx dimerization from maintenance of MEK-ERK1/2 signaling. Furthermore, we show BRAF V600E ΔEx association with its substrate, MEK, is enhanced and required for RAF inhibitor resistance. RAF inhibitor treatment increased phosphorylation at serine 729 (S729) in BRAF V600E ΔEx. Mutation of S729 to a non-phosphorylatable residue reduced BRAF V600E ΔEx-MEK interaction, reduced dimerization or oligomerization, and increased RAF inhibitor sensitivity. Conversely, mutation of the BRAF dimerization domain elicited partial effects on MEK association and RAF inhibitor sensitivity. Our data implicate BRAF S729 in resistance to RAF inhibitor and underscore the importance of substrate association with BRAF V600E ΔEx. These findings may provide opportunities to target resistance driven by aberrantly spliced forms of BRAF V600E.
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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.